Nonpolar Atoms Research Articles

Challenges in Protein QM/MM Simulations with Intra-Backbone Link Atoms.

Hybrid quantum mechanical/molecular mechanical (QM/MM) simulations fuel discoveries in many fields of science including computational biochemistry and enzymology. Development of more convenient tools leads to an increase in the number of works in which mechanical insights into enzymes' mode of operation are obtained. Most commonly, these tools feature hydrogen-capping (link atom) approach to provide coupling between QM and MM subsystems across a covalent bond. Extensive studies were conducted to provide a solid foundation for the correctness of such an approach when a bond to a nonpolar MM atom is considered. However, not every task may be accomplished this way. Certain scenarios of using QM/MM in computational enzymology encourage or even necessitate the incorporation of backbone atoms into the QM region. Two out of three backbone atoms are polar, and in QM/MM with electrostatic embedding, a neighboring link atom will be hyperpolarized. Several schemes to mitigate this effect were previously proposed alongside a rigorous assessment of quantitative effects on model systems. However, it was not clear whether they may translate into qualitatively different results and how link atom hyperpolarization may manifest itself in a real-life enzymological scenario. Here, we show that the consequences of such an artifact may be severe and may completely overturn the conclusions drawn from the simulations. Our case advocates for the use of charge redistribution schemes whenever intra-backbone QM/MM boundaries are considered. Moreover, we addressed how different boundary types and charge redistribution schemes influence backbone dynamics. We showed that the results are heavily dependent on which boundary MM terms are retained, with charge alteration being of secondary importance. In the worst case, only three intra-backbone boundaries may be used with relative confidence in the adequacy of resulting simulations, irrespective of the hyperpolarization mitigation scheme. Thus, advances in the field are certainly needed to fuel new discoveries. As of now, we believe that issues raised in this work might encourage authors in the field to report what boundaries, boundary MM terms, and charge redistribution schemes they are using, so their results may be correctly interpreted.

The curvature effect on the distribution behavior of nonpolar atoms in nano-confined space.

The chemical and physical properties of nonpolar atoms are obviously affected by confinement. A curvature-based theoretical model for helium particles distributed in carbon nanotubes is proposed by considering the L-J pair potential and the Boltzmann distribution. The potential gap formed by the non-bonded interaction between a helium atom and a carbon nanotube surface leads to a layered structure distribution with high density near the surface. By assuming adsorption as a competition between the potential gap and the thermal energy, the desorption critical temperature is discussed for helium adsorbed on the layer, which is confirmed to be a monotonic decreasing function of nanotube diameter. The helium atom distribution relations between the nanotube diameter, temperature and the potential gap obtained from molecular dynamics simulations are consistent with the curvature-based model predictions. The adsorption ratio is defined by the numbers of particles adsorbed on the near surface layered structure over total particle numbers, which decreases with the increase of temperature and carbon nanotube diameter. The curvature-based model is further confirmed by studying krypton and argon atoms in the appendix. This work provides a simple model to predict the distribution behavior and reveals the curvature effect on the distribution and adsorption of non-polar atoms confined in nano-space, which could be important for a better understanding of the chemical and physical properties of gas storage in the nano-confined space.

Molecular docking and in vitro experiments verified that kaempferol induced apoptosis and inhibited human HepG2 cell proliferation by targeting BAX, CDK1, and JUN.

Hepatocellular carcinoma, as a common liver cirrhosis complication, has become the sixth most common cancer worldwide, and its increasing incidence has resulted in considerable medical and economic burdens. As a natural polyphenolic compound, kaempferol has exhibits a wide range of antitumor activities against multiple cancer targets. In this study, the Autodock software was used for molecular docking to simulate the interaction process between kaempferol and HCC targets and the PyMOL software was used for visualization. Proliferation of kaempferol HepG2 cells under the effect of kaempferol was detected using Cell Counting Kit-8 (CCK-8) assay, and the apoptosis rate of HepG2 cells was detected using flow cytometry. The expressions of proteins BAX, CDK1, and JUN protein expressions were detected by Western blot. Molecular docking found that the kaempferol ligand has 3 rotatable bonds, 6 nonpolar hydrogen atoms, and 12 aromatic carbon atoms, and can form complexes with the kaempferol targets P53, BAX, AR, CDK1, and JUN through electrostatic energy. GO (Gene Ontology) enrichment analysis suggests that kaempferol regulates the biological function of hepatocellular carcinoma cells and is related to apoptosis. Cell Counting Kit-8 assay suggested that Kaempferol can significantly inhibited HepG2 cell proliferation, and the inhibition rate increased with the increase in drug concentration and incubation time. Moreover, kaempferol can promoted HepG2 cell apoptosis in a dose-dependent manner. This compound upregulated BAX and JUN expression and downregulated CDK1 expression. Thus, Kaempferol can promote HepG2 cell apoptosis, and the regulatory mechanism may be related to the regulation of the expression levels of the apoptosis-related proteins BAX, CDK1, and JUN.

Couette flows between various bounding substrates

Molecular dynamics simulations of equilibrium structures and Couette flows of polar water molecules and nonpolar argon atoms between bounding carbon substrates disposed at the distance h=1.5 nm from each other have been performed. Two symmetric configurations when both substrates have similar, either graphene - like crystalline or amorphous structures, and one asymmetric configuration consisted of one substrate with graphene - like crystalline structure and another substrate with amorphous structure have been considered. It has been found that, in all configurations under consideration, the Couette flow velocity profiles depend strongly on polarity of fluid particles confined between bounding substrates. It has been also found that, for substrates with different structures, the Couette flows depend strongly on which of the substrate is moving and which is fixed.

Equilibrium structures and flows of polar and nonpolar liquids and their mixtures in carbon nanotubes with rectangular cross sections

Molecular dynamics (MD) simulations of equilibrium structures and flows of polar water, nonpolar argon and methane, and mixtures of water and methane confined by single-walled carbon nanotubes (SWCNTs) with different rectangular cross sections have been performed. The results of these simulations show that equilibrium structures and flows of all confined liquids significantly depend not only on the shape of the SWCNT’s rectangular cross sections but also on the types of liquids inside SWCNTs. The cross sections of equilibrium structures of all confined liquids resemble replicas of cross sections of corresponding SWCNTs. In addition, the equilibrium structures formed by nonpolar argon atoms are most spatially ordered whereas nonpolar water molecules form the least spatially ordered equilibrium structures. It has been found that, for nonpolar methane flows through SWCNTs with rectangular cross sections, there are critical values fxc of the external driving force below which an average flow velocity is equal to nearly zero and above fxc methane molecules can flow. The critical value of the external driving force depends strongly on the shape of rectangular cross sections of SWCNTs under consideration. It has been also found that, for a sufficiently large value of the external driving force, the liquid argon flow through SWCNT with rectangular cross section with the ratio between its sides 1:4 demonstrates the ballistic frictionless regime.

Superfluidity inside carbon nanotubes.

Molecular dynamics simulations of equilibrium structures and flows of nonpolar argon atoms confined by single-walled carbon nanotubes (SWCNTs) with circular cross section and rectangular cross section having the same area and the ratio between its sides 1:4 have been performed. It has been shown that, inside these SWCNTs, argon atoms form the spatially ordered structures and, under action of external driving forces they move collectively along SWCNT's axes. It has been also obtained that there are two regimes of such collective movement. In the first regime, when the driving external force f_{x0} is lower than a certain critical value f_{xc}, argon atoms flow through these SWCNTs with the finite average flow velocity. In the second regime, when the driving external force f_{x0} exceeds f_{xc}, the retarding friction force acting on argon atoms from bounding wall carbon atoms gradually drops to zero and the average flow velocity exhibits an unlimited growth. Moreover, when the retarding friction force becomes close to zero, the fluid will continue to flow with the same constant velocity at switched off external driving force. Hence, in the second regime, argon atoms inside the above-mentioned SWCNTs demonstrate the ballistic frictionless flows which resemble the superfluidic liquid flow. It has been shown that collective frictionless ballistic flows of argon atoms through SWCNTs are caused by the crystalline structure of SWCNT's bounding walls and, for the same SWCNTs with random distribution of carbon atoms on the bounding walls, one can observe only the first regime of the argon atom flows.

Relevance of silica surface morphology in Ampyra adsorption. Insights from quantum chemical calculations.

Theoretical calculations are performed using the Vienna Ab-initio simulation package (VASP) to understand the mechanisms that control the adsorption of Ampyra drug on the different crystallographic planes of β-cristobalite: the hydroxylated (111) and (100) surfaces. The Ampyra-silica interaction is most favored on the (100) surface where the entire ring of the molecule interacts with the surface while on the (111) face, lesser exchange and fewer non-polar atoms are involved. Calculations show that the interactions mainly occur at the interface between the Ampyra and the closest silanol groups, according to the formation of the H-bonding interactions. The results indicate that the H-bonds have an important influence on the adsorption of the Ampyra. In consequence, adsorption on the (111) surface is observed to a lesser extent than on the (100) surface according the smaller hydroxyl density.

Using molecular dynamics simulations to identify the key factors responsible for chiral recognition by an amino acid-based molecular micelle

Molecular dynamics (MD) simulations were used to investigate the binding of six chiral compounds to the amino acid-based molecular micelle (MM) poly-(sodium undecyl-(L)-leucine-leucine) or poly(SULL). The MM investigated is used as a chiral selector in capillary electrophoresis. The project goal was to characterize the chiral recognition mechanism in these separations and to move toward predictive models to identify the best amino acid-based MM for a given separation. Poly(SULL) was found to contain six binding sites into which chiral compounds could insert. Four sites had similar sizes, shapes, and electrostatic properties. Enantiomers of alprenolol, propranolol, 1,1′-bi-2-naphthyl-2,2′-diyl hydrogen phosphate, 1,1′-bi-2-naphthol, chlorthalidone, or lorazepam were separately docked into each binding pocket and MD simulations with the resulting intermolecular complexes were performed. Solvent-accessible surface area calculations showed the compounds preferentially associated with binding sites where they penetrated into the MM core and shielded their non-polar atoms from solvent. Furthermore, with five of the six compounds the enantiomer with the most favorable free energy of MM association also experienced the most favorable intermolecular hydrogen bonding interactions with the MM. This result suggests that stereoselective intermolecular hydrogen bonds play an important role in chiral discrimination in separations using amino acid-based MMs.GRAPHICAL ABSTRACT

Hydration Water Distribution around Intrinsically Disordered Proteins

The distribution and local structural order of hydration water in the proximity of intrinsically disordered proteins/regions are investigated within the frame work of three-dimensional (3D)-reference interaction site model theory. The hydration water distribution around the protein surface is quantified in terms of the 3D distribution function and the water-protein radial distribution function (RDF), whereas the local ordering of water molecules around the protein surface is measured in terms of the tetrahedral order parameter. To the best of our knowledge, this is the first theoretical study of the 3D hydration water distribution profiles of disordered proteins. The analysis of the 3D hydration profiles reveals a nonuniform distribution and higher hydration water density around disordered proteins as compared to the globular ones because of their noncompact structures with more solvent-accessible surface area and the abundance of charged residues. This difference is also evident in the residue-specific RDFs of water around different polar and nonpolar atoms of charged and hydrophobic residues of the globular and disordered proteins. The average tetrahedral order parameter evaluated as a function of the water-water distance shows that water molecules are more ordered around disordered regions/proteins because of their higher mean net charge facilitating stronger water-protein interactions.

Large-Scale Bose-Einstein Condensation in an Atomic Gas by Applying an Electric Field

Large-scale Bose-Einstein condensation (BEC) of cesium atoms has been observed (T=343K). The technical bottleneck of BEC is very small trapping volume (10-8cm3), which made the number of condensed atoms still stagnant (less than 107), much smaller than normal condensation (more than 1013), large-scale BEC has never been observed. In BEC experiment, scientists have applied magnetic field (used to trap atoms) and laser (used to cool atoms), but never considered applying electric field, because they think that all kinds of atoms are non-polar atoms. The breakthrough of the bottleneck lies in the application of electric field. In theory, despite 6s and 6p states of cesium are not degenerate, but Cs may be polar atom doesn't conflict with quantum mechanics because it is hydrogen-like atom. When an electric field was applied, Cs atoms become dipoles, therefore large-scale BEC can be observed. BEC experiment of cesium has been redone. From the entropy S=0, critical voltage Vc=78V. When V 0; when V > Vc, S Vc, almost all Cs atoms (bosons) are in exactly the same state，according to Feynman, “the quantum physics is the same thing as the classical physics”, so our classical theory can explain BEC experiment satisfactorily. Ultra-low temperature is to make Bose gas phase transition, we used critical voltage to achieve phase transition, ultra-low temperature is no longer necessary. Five innovative formulas were first reported in the history of physics, the publication of this article marking mankind will enter a new era of polar atoms.

Full Protein Sequence Redesign with an MMGBSA Energy Function.

Computational protein design aims to create proteins with novel properties. A key element is the energy or scoring function used to select the sequences and conformations. We study the performance of an "MMGBSA" energy function, which combines molecular mechanics terms, a generalized Born and surface area (GBSA) solvent model, with approximations that make the model pairwise additive. Our approach is implemented in the Proteus software. The use of a physics-based energy function ensures a certain model transferability and explanatory power. As a first test, we redesign the sequence of nine proteins, one position at a time, with the rest of the protein having its native sequence and crystallographic conformation. As a second test, all positions are designed together. The contributions of individual energy terms are evaluated, and various parametrizations are compared. We find that the GB term significantly improves the results compared to simple Coulomb electrostatics but is affected by pairwise decomposition errors when all positions are designed together. The SA term, with distinct energy coefficients for nonpolar and polar atoms, makes a decisive contribution to obtain realistic protein sequences and can partially compensate for the absence of a GB term. With the best GBSA protocol, we obtain nativelike protein cores and Superfamily recognition of almost all of our sequences.

Polyphenols rich Passiflora leschenaultii leaves modulating Farnesoid X Receptor and Pregnane X Receptor against paracetamol-induced hepatotoxicity in rats.

The hepatoprotective effect of P. leschenaultii. (DC) leaves was investigated in rats under paracetamol induced oxidative stress. Leaf acetone extract (200 and 400mg/kg) were administered daily via gavage for 14days before paracetamol (2000mg/kg, p.o.) treatment. After the experiment, the levels of serum biochemical parameters and enzymatic antioxidant levels were determined. Furthermore, liver tissues were analyzed histopathologically. Additionally, the molecular docking studies of the identified compounds against PXR and FXR proteins were also performed. The assessment revealed that the acetone extract significantly reduced the elevated levels of SGPT, SGOT and ALP in serum. Moreover, the enzymatic antioxidants such as SOD, CAT and LPO were also retained normally by the plant extract. From histopathological analysis, it was clearly evident that the cellular architecture of plant extract treated rat liver tissues were not affected by the paracetamol induction at the higher dose. The results of docking studies also revealed that the identified compounds showed steric interactions (between nonpolar atoms) with amino acid groups. Collectively, the present study suggests that P. leschenaultii leaves extract protects the liver from paracetamol induced hepatic damage.

Theoretical and Experimental Proof of Alkali-Metal Atom as Polar Atom

In addition to polar molecules, there is no polar atom in the natural world, which is a deep-rooted traditional concept that has lasted for more than a century. However, our research showed that alkali-metal atoms form an exception. In theory, we proved that alkali atom may be polar atom doesn't conflict with quantum mechanics, which is a great breakthrough in measurement theory of quantum mechanics. Variation of the capacitance with temperature and density offers a means of separating polar and nonpolar atom, but no one has done these experiments so far. If alkali atom is nonpolar atom, its capacitance should be independent of temperature and density, because atomic nucleus located at the center of the electron cloud. Our experiments showed that Na, K, Rb and Cs atoms are polar atoms, because their capacitance is not only related to temperature, but also to density. Unlike alkali atoms, the capacitance of Hg gas is independent of temperature and density, so mercury is nonpolar atom. Therefore atoms can be divided into two categories: polar and nonpolar atom, this discovery will lead to an exciting revolution in Bose- Einstein condensation (BEC) research and condensed matter physics. BEC experiments have been carried out for decades, but the number of condensed atoms is still very small (<107) because scientists has never applied an electric field. Our innovation lies in the application of an electric field, we don't need magnetic field and lasers. When V=390 volts, condensates contained up to 2.51 × 1017 sodium atoms; when V=350 volts, condensates contained up to 1.93 × 1017 cesium atoms, large-scale BEC at T=343 K or 353 K has been observed. Now scientists generally assume that polar molecules may be used as candidate materials for quantum computers. In the future, polar atoms will replace polar molecules as candidate materials for quantum computers, because of its very small moment of inertia.

DNA minor groove electrostatic potential: influence of sequence-specific transitions of the torsion angle gamma and deoxyribose conformations

The structural adjustments of the sugar-phosphate DNA backbone (switching of the γ angle (O5′–C5′–C4′–C3′) from canonical to alternative conformations and/or C2′-endo → C3′-endo transition of deoxyribose) lead to the sequence-specific changes in accessible surface area of both polar and non-polar atoms of the grooves and the polar/hydrophobic profile of the latter ones. The distribution of the minor groove electrostatic potential is likely to be changing as a result of such conformational rearrangements in sugar-phosphate DNA backbone. Our analysis of the crystal structures of the short free DNA fragments and calculation of their electrostatic potentials allowed us to determine: (1) the number of classical and alternative γ angle conformations in the free B-DNA; (2) changes in the minor groove electrostatic potential, depending on the conformation of the sugar-phosphate DNA backbone; (3) the effect of the DNA sequence on the minor groove electrostatic potential. We have demonstrated that the structural adjustments of the DNA double helix (the conformations of the sugar-phosphate backbone and the minor groove dimensions) induce changes in the distribution of the minor groove electrostatic potential and are sequence-specific. Therefore, these features of the minor groove sizes and distribution of minor groove electrostatic potential can be used as a signal for recognition of the target DNA sequence by protein in the implementation of the indirect readout mechanism.

Bose–Einstein condensation in a vapor of sodium atoms in an electric field

Bose–Einstein condensation (BEC) at normal temperature (T=343K) has been observed because an electric field was first applied. There are two ways to achieve phase transition: lower the temperature of Bose gas or increase its density. This article provides more appropriate method: increase the voltage. In theory, 3s and 3p states of sodium are not degenerate, but Na may be polar atom doesnot conflict with quantum mechanics because it is hydrogen-like atom. Our innovation lies in we applied an electric field used for the orientation polarization. Na vapor was filled in a cylindrical capacitor. In order to determine the polarity of sodium, we measured the capacitance at different temperatures. If Na is non-polar atom, its capacitance should be independent of temperature because the nucleus of atom is located at the center of the electron cloud. But our experiment shows that its capacitance is related to temperature, so Na is polar atom. In order to achieve Na vapor phase transition, we measured the capacitance at different voltages. From the entropy of Na vapor S=0, the critical voltage Vc=68volts. When V<Vc, many atoms are in random orientation S>0; when V>Vc, the atoms become aligned with the field S<0, phase transition occurred. When V=390volts »Vc, the capacitance decreased from C=1.9C0 to C≈C0 (C0 is the vacuum capacitance), this result implies that almost all the Na atoms (more than 98%) are aligned with the field, Na vapor entered quasi-vacuum state. We create a BEC with 2.506×1017 atoms, condensate fraction reached 98.9%. This is BEC in momentum space. Our experiment shows that if a Bose gas enters quasi-vacuum state, this also means that it underwent phase transition and generates BEC. Therefore, quasi-vacuum state of alkali gas is essentially large-scale BEC. This is an unexpected discovery. BEC and vacuum theory are two unrelated research areas, but now they are closely linked together. The maximum induced dipole moment dind≤7.8×10−15ecm can be neglected. Ultra-low temperature is in order to make Bose gas phase transition, we achieve the phase transition by the critical voltage, so the ultra-low temperature is not necessary. According to the standard proposed by Ketterle, although we didn’t use laser cooling atoms, our experiment is real ideal BEC. Na material with purity 99.95% was supplied by Strem Chemicals Co., USA. Our experiments are easily repeated because low temperature is not necessary.

Large-Scale Bose-Einstein Condensation in a Vapor of Cesium Atoms at Normal Temperature (T=353K)

Large-scale BEC of cesium at T=353 K was first observed. Until now, scientists have applied magnetic fields and lasers, but never applied electric fields, and atoms are oriented at random, so observation of BEC is very difficult. Our innovation lies in the application of electric fields. We theoretically proved that alkali atom (include Cs) may be polar atom doesn't conflict with quantum mechanics. Variation of the capacitance with temperature offers a means of separating the polar and non-polar atom. Cs vapor was filled in cylindrical capacitor. Our experiment shows that Cs is polar atom because its capacitance is related to temperature. In the past, to realize the phase transition, ultralow temperature is necessary. But now we don’t require ultralow temperature, because we use the critical voltage Vc to achieve the phase transition. From the entropy S=Nk ln 2πe /a=0, a=dV/kTH =2πe, Vc ≈ 63volts. When V 0; when V >Vc, S < 0, phase transition occurred. When V=350 volts, the capacitance decreased from C=1.97C0 to C ≈ C0 (C0 is the vacuum capacitance), this result implies that almost all Cs atoms (more than 98.9%), like as dipoles, are aligned with the field. We create BEC with 1.928×1017 atoms, these atoms have the same momentum. Cs material with purity 99.95% was supplied by Strem Chemicals Co., USA. Both BEC and superconductivity are condensed in the momentum space, therefore these two kinds of condensation can’t be observed with the naked eye. When superconductivity occurs, the resistance R≈0, a simple and direct method to observe superconductivity is to measure the resistance by voltammetry. Similarly, when BEC occurs, the electric susceptibility χe=C/C0 –1 ≈ 0, a simple and direct method to observe BEC is to measure the capacitance by cylindrical capacitor. BEC is also a quasi-superconducting state.

Confinement effects on liquid-flow characteristics in carbon nanotubes

Liquid flow dynamics through the armchair (6,6)-(160,160) carbon nanotubes (CNTs) is elucidated by molecular dynamics simulations. The liquid is modeled by nonpolar argon atoms to understand the fundamental flow physics. The velocity profiles and slip lengths are discussed considering the radial distributions of the fluid density by the presently proposed finite difference-based velocity fitting method. It is found that as the CNT diameter D increases, the slip length and the flow rate enhancement show three-step transitional profiles in the region of D≤2.3 nm. The slip length and the flow rate stepwise increase at the first transition while they drop at the second and third transitions. The first transition corresponds to the structural change from the single-file chain to single-ring structures of the molecule cluster. The second and third transitions take place when the ring structure starts to develop another inner layer.

Computational design of enzyme-ligand binding using a combined energy function and deterministic sequence optimization algorithm.

Enzyme amino-acid sequences at ligand-binding interfaces are evolutionarily optimized for reactions, and the natural conformation of an enzyme-ligand complex must have a low free energy relative to alternative conformations in native-like or non-native sequences. Based on this assumption, a combined energy function was developed for enzyme design and then evaluated by recapitulating native enzyme sequences at ligand-binding interfaces for 10 enzyme-ligand complexes. In this energy function, the electrostatic interaction between polar or charged atoms at buried interfaces is described by an explicitly orientation-dependent hydrogen-bonding potential and a pairwise-decomposable generalized Born model based on the general side chain in the protein design framework. The energy function is augmented with a pairwise surface-area based hydrophobic contribution for nonpolar atom burial. Using this function, on average, 78% of the amino acids at ligand-binding sites were predicted correctly in the minimum-energy sequences, whereas 84% were predicted correctly in the most-similar sequences, which were selected from the top 20 sequences for each enzyme-ligand complex. Hydrogen bonds at the enzyme-ligand binding interfaces in the 10 complexes were usually recovered with the correct geometries. The binding energies calculated using the combined energy function helped to discriminate the active sequences from a pool of alternative sequences that were generated by repeatedly solving a series of mixed-integer linear programming problems for sequence selection with increasing integer cuts.

An electronic environment and contact direction sensitive scoring function for predicting affinities of protein–ligand complexes in Contour®

Contour® is a computational structure-based drug design technology that grows drug-like molecules by assembling context sensitive fragments in well-defined binding pockets. The grown molecules are scored by a novel empirical scoring function developed using high-resolution crystal structures of diverse classes of protein–ligand complexes and associated experimental binding affinities. An atomic model bearing features of the valence bond and VSEPR theories embodying their molecular electronic environment has been developed for non-covalent intermolecular interactions. On the basis of atomic hybridization and polarization states, each atom is modeled by features representing electron lone pairs, p-orbitals, and polar and non-polar hydrogens. A simple formal charge model was used to differentiate between polar and non-polar atoms. The interaction energy and the desolvation contribution of the protein–ligand association energy is computed as a linear sum of pair-wise interactions and desolvation terms. The pair-wise interaction energy captures short-range positive electrostatic interactions via hydrogen bonds, electrostatic repulsion of like charges, and non-bond contacts. The desolvation energy is estimated by calculating the energy required to desolvate interaction surfaces of the protein and the ligand in the complex. The scoring function predicts binding energies of a diverse set of protein–ligand complexes used for training with a correlation coefficient of 0.61. It also performs equally well in predicting association energies of a diverse validation set of protein–ligand complexes with a correlation coefficient of 0.57, which is equivalent to or better than 12 other scoring functions tested against this set including X-Score, GOLD, and DrugScore.

Predicting Enzyme Adsorption to Lignin Films by Calculating Enzyme Surface Hydrophobicity

The inhibitory action of lignin on cellulase cocktails is a major challenge to the biological saccharification of plant cell wall polysaccharides. Although the mechanism remains unclear, hydrophobic interactions between enzymes and lignin are hypothesized to drive adsorption. Here we evaluate the role of hydrophobic interactions in enzyme-lignin binding. The hydrophobicity of the enzyme surface was quantified using an estimation of the clustering of nonpolar atoms, identifying potential interaction sites. The adsorption of enzymes to lignin surfaces, measured using the quartz crystal microbalance, correlates to the hydrophobic cluster scores. Further, these results suggest a minimum hydrophobic cluster size for a protein to preferentially adsorb to lignin. The impact of electrostatic contribution was ruled out by comparing the isoelectric point (pI) values to the adsorption of proteins to lignin surfaces. These results demonstrate the ability to predict enzyme-lignin adsorption and could potentially be used to design improved cellulase cocktails, thus lowering the overall cost of biofuel production.