Presence Of Explicit Water Molecules Research Articles

Antioxidant and anticancer properties of plant‐based bioactive flavonoids cardamonin and alpinetin: A theoretical insight from •OOH antiradical and Cu (II) chelation mechanisms

AbstractA density functional theory (DFT) study aimed at a comparative investigation on the antioxidant mechanisms of cardamonin and alpinetin, two flavonoid bioactive components derived from plant sources with potential medicinal properties, has been performed through assessment of their •OOH scavenging ability in non‐polar medium and Cu (II) chelation ability in the absence and presence of explicit water molecules stabilising the metal cation. In addition, a comparison of the antioxidant properties of cardamonin with the moiety of phloroglucinol and acylated phloroglucinol has been performed to establish cardamonin's antioxidant potentiality among the phloroglucinol family of compounds. The results of the investigation reveal that alpinetin could be considered a better radical scavenger than cardamonin within the non‐polar lipid bilayer medium of biological systems. However, the role of both compounds as •OOH scavengers may be limited, in comparison to standard antioxidant molecules, such as α‐tocopherol, because of the fact that the bond dissociation enthalpy for the hydrogen atom abstraction mechanism has a positive value, which signifies that the radical scavenging mechanism is not a thermodynamically preferred reaction. Cardamonin is found also to be a weaker antioxidant molecule than phloroglucinol and acylated phloroglucinol moieties. In terms of metal chelation mechanism, cardamonin is a better Cu (II) chelator than alpinetin since it has a higher metal ion affinity than alpinetin upon coordination to the Cu (II) cation. The results obtained could also imply that cardamonin is a better agent in dealing with angiogenesis, tumour growth and metastatis stages of cancer than alpinetin, since the ability of chelating metal cation shown by cardamonin ascribes it a better role as an anticancer agent than alpinetin. Therefore, although alpinetin may prove to play an important role as a promising antioxidant and antiinflamatory agent than cardamonin, by scavenging radical species, cardamonin would prove more valuable in the control of various stages of cancer growth than alpinetin.

EXPRORER: Rational Cosolvent Set Construction Method for Cosolvent Molecular Dynamics Using Large-Scale Computation.

Cosolvent molecular dynamics (CMD) simulations involve an MD simulation of a protein in the presence of explicit water molecules mixed with cosolvent molecules to perform hotspot detection, binding site identification, and binding energy estimation, while other existing methods (e.g., MixMD, SILCS, and MDmix) utilize small molecules that represent functional groups of compounds. However, the cosolvent selections employed in these methods differ and there are only a few cosolvents that are commonly used in these methods. In this study, we proposed a systematic method for constructing a set of cosolvents for drug discovery, termed the EXtended PRObes set construction by REpresentative Retrieval (EXPRORER). First, we extracted typical substructures from FDA-approved drugs, generated 138 cosolvent structures, and for each cosolvent molecule, we conducted CMD simulations to generate a spatial probability distribution map of cosolvent atoms (PMAP). Analyses of PMAP similarity revealed that a cosolvent pair with a PMAP similarity greater than 0.70-0.75 shared similar structural features. We present a method for the construction of a cosolvent subset that satisfies a similarity threshold for all cosolvents, and we tested the constructed sets for four proteins. To our knowledge, this is the first study to include a systematic proposal for cosolvent set construction, and thus, the EXPRORER cosolvents will provide deeper insights into ligand binding sites of various proteins.

Understanding the influence of external perturbation on aziridinium ion formation

ABSTRACT A density functional theory study is performed to understand the effect of discrete water molecules during Az+ ion formation in nitrogen mustards. A comparative study in gas phase, and implicit and explicit solvation models of three drug molecules (mustine, chlorambucil and melphalan) is reported. Noteworthy changes in the structure and C–N stretching frequencies of the transition states have been observed in the presence of explicit water molecules. Presence of explicit water molecules reduces the positive charge around the tricyclic Az+ ring, and hence stabilising it. Both activation energy and rate constants are seen to be significantly affected in the presence of discrete water molecules.

Electronic properties of carbon nanotubes complexed with a DNA nucleotide.

Electronic properties of carbon nanotubes (CNTs) play an important role in their interactions with nano-structured materials. In this work, interactions of adenosine monophosphate (AMP), a DNA nucleotide, with metallic and semi-conducting CNTs are studied using the density functional tight binding (DFTB) method. The electronic structure of semi-conducting CNTs was found to be changed as they turned to metallic CNTs in a vacuum upon interaction with the nucleotide while metallic CNTs remain metallic. Specifically, the band gap of semi-conducting CNTs was decreased by 0.79 eV on average while nearly no change was found in the metallic tubes. However, our investigations showed that the presence of explicit water molecules prevents the metallicity change and only small changes in the CNT band gap occur. According to our charge analysis, the average negative charge accumulated on CNTs upon interaction with the AMP was determined to be 0.77 e in a vacuum while it was 0.03 e in solution. Therefore, it is essential to include explicit water molecules in simulating complexes formed by DNA nucleotides and CNTs which were ignored in several past studies performed using quantum mechanical approaches.

Radicalization and Radical Catalysis of Biomass Sugars: Insights from First-principles Studies.

Ab initio and density functional calculations are conducted to investigate the radicalization processes and radical catalysis of biomass sugars. Structural alterations due to radicalization generally focus on the radicalized sites, and radicalization affects H-bonds in D-fructofuranose more than in D-glucopyranose, potentially with outcome of new H-bonds. Performances of different functionals and basis sets are evaluated for all radicalization processes, and enthalpy changes and Gibbs free energies for these processes are presented with high accuracy, which can be referenced for subsequent experimental and theoretical studies. It shows that radicalization can be utilized for direct transformation of biomass sugars, and for each sugar, C rather than O sites are always preferred for radicalization, thus suggesting the possibility to activate C-H bonds of biomass sugars. Radical catalysis is further combined with Brønsted acids, and it clearly states that functionalization fundamentally regulates the catalytic effects of biomass sugars. In presence of explicit water molecules, functionalization significantly affects the activation barriers and reaction energies of protonation rather than dehydration steps. Tertiary butyl and phenyl groups with large steric hindrances or hydroxyl and amino groups resulting in high stabilities for protonation products drive the protonation steps to occur facilely at ambient conditions.

A computational study of the chlorination and hydroxylation of amines by hypochlorous acid.

The reactions of hypochlorous acid (HOCl) with ammonia, (di)methylamine, and heterocyclic amines have been studied computationally using double-hybrid DFT methods (B2PLYP-D and BK-PLYP) and a G3B3 composite scheme. In the gas phase the calculated energy barriers for N- and/or C-hydroxylation are ca. 100 kJ mol(-1) lower than the barrier for N-chlorination of amines. In the model solvent, however, the latter process becomes kinetically more favored. The explicit solvent effects are crucial for determination of the reaction mechanism. The N-chlorination is extremely susceptible to the presence of explicit water molecules, while no beneficial solvation effect has been found for the N- or C-hydroxylation of amines. The origin of the observed solvent effects arises from differential solvation of the respective transition states for chlorine- and oxygen-transfers, respectively. The nature of solvation of the transition state structures has been explored in more detail by classical molecular dynamics (MD) simulation. In agreement with the quantum mechanical approach, the most stable structural motif, which includes the amine, HOCl, and two reactive waters, has been identified during the MD simulation. The inclusion of 5 or 6 explicit water molecules is required to reproduce the experimental barriers for HOCl-induced formation of N-chloramines in an aqueous environment.

A computational study of the factors affecting the electrical conductance of long chain n-porphyrin di-thiols

There has been much interest in the study of quantum transport in molecular nanowires due to their possible importance in molecular electronic devices. As the devices become smaller, it is important to understand the factors that govern the electrical conductance across single molecules. At the current time it is not possible to carry out ab initio calculations on all of these molecular systems due to the heavy computational demands. In this paper, we show that a semi-empirical approach, the self-consistent extended Hückel method (SC-EHM), gives results for small molecular systems that compare favourably with computations based on density functional theory and so may be used in the study of larger systems.We have used the SC-EHM to investigate the effect of various factors on the conductance of the n-porphyrin molecules. In particular, we have studied how the conductance varies with the length of the n-porphyrin molecule, the metal atom in the porphyrin ring and the presence of explicit water molecules. We find that the water molecules induce a change in the work function at the gold electrodes causing a shift in the features in the electron density of states which in turn enhance the conductance. The attenuation of the conductance with length for this system is found to be in accordance with the results of other workers.

Binding of NDGA and morin with phospholipase A2: experimental and computational evidences

The effects of morin and nordihydroguaiaretic acid (NDGA), two plant secondary metabolites, on porcine pancreatic phospholipase A2 (PLA2) were investigated by isothermal titration calorimetry (ITC) and in silico docking analyses. The binding energies obtained for NDGA and morin from the ITC studies are − 6.36 and − 5.91 kcal mol− 1, respectively. Similarly, the glide scores obtained for NDGA and morin towards PLA2 were − 7.32 and − 7.23 kcal mol− 1, respectively. Further the docked complexes were subjected to MD simulation in the presence of explicit water molecules to check the binding stability of the ligands in the active site of PLA2. The bound ligands make hydrogen bonds with the active site residues of the enzyme and coordinate bonds with catalytically important Ca2+ ion. The binding of ligands at the active site of PLA2 may also contribute to the reported anti-inflammatory properties of NDGA and morin.

Structural, Electronic, and Optical Properties of Metallo Base Pairs in Duplex DNA: A Theoretical Insight

Using density functional theory calculations, we investigated the structural, energetic, electronic, and optical properties of recently synthesized duplex DNA containing metal-mediated base pairs. The studied duplex DNA consists of three imidazole (Im) units linked through metal (Im-M-Im, M = metal) and four flanking A:T base pairs (two on each side). We examined the role of artificial base pairing in the presence of two distinctive metal ions, diamagnetic Ag(+) and magnetic Cu(2+) ions, on the stability of duplex DNA. We found that metal-mediated base pairs form stable duplex DNA by direct metal ion coordination to the Im bases. Our results suggest a higher binding stability of base pairing mediated by Cu(2+) ions than by Ag(+) ions, which is attributed to a larger extent of orbital hybridization. We furthermore found that DNA modified with Im-Ag(+)-Im shows the low-energy optical absorption characteristic of π-π*orbital transition of WC A:T base pairs. On the other hand, we found that the low-energy optical absorption peaks for DNA modified with Im-Cu(2+)-Im originate from spin-spin interactions. Additionally, this complex exhibits weak ferromagnetic coupling between Cu(2+) ions and strong spin polarization, which could be used for memory devices. Moreover, analyzing the role of counter ions (Na(+)) and the presence of explicit water molecules on the structural stability and electronic properties of the DNA duplex modified with Im-Ag(+)-Im, we found that the impact of these two factors is negligible. Our results are fruitful for understanding the experimental data and suggest a potential route for constructing effective metal-mediated base pairs in duplex DNA for optoelectronic applications.

Microsolvation and hydrogen bond interactions in Glycine Dipeptide: Molecular dynamics and density functional theory studies

Molecular dynamics (MD) simulations were carried out to study the conformational characteristics of Glycine Dipeptide (GD) in the presence of explicit water molecules for over 10ns with a MD time step of 2fs. The density functional theory (DFT) methods with 6-311G** basis set have been employed to study the effects of microsolvation on the conformations of GD with 5–10 water molecules. The interaction energy with BSSE corrections and the strength of the intermolecular hydrogen bond interactions have been analyzed. The Bader's Atoms in Molecules (AIM) theory has been employed to investigate H-bonding patterns in water interacting complexes. The natural bond orbital (NBO) analysis has been carried out to analyze the charge transfer between proton acceptor to the antibonding orbital of the XH bond in the hydrated complexes. NMR calculations have been carried out at B3LYP/6-311G (2d, 2p) level of theory to analyse the changes in structure and hydrogen bonding environment that occur upon solvation.

Molecular Interactions of Alzheimer's Aβ Protofilaments with Lipid Membranes

Amyloid fibrils and peptide oligomers play central roles in the pathology of Alzheimer's disease, type 2 diabetes, Parkinson's disease, Huntington's disease, and prion-related disease. Here, we investigate the molecular interactions between preformed amyloid β (Aβ) molecular protofilaments and lipid bilayer membranes, in the presence of explicit water molecules, using computational models and all-atom molecular dynamics. These interactions play an important role in the stability and function of both Aβ fibrils and the adjacent cellular membrane. Taking advantage of the symmetry-related and directional properties of the protofilaments, we build models that cover several relative protofilament–membrane orientations. Our molecular dynamics simulations reveal the relative contributions of different structural elements to the dynamics and stability of Aβ protofilament segments near membranes, and the first steps in the mechanism of fibril–membrane interactions. During this process, we observe a significant alteration of the side-chain contact pattern in protofilaments, although a fraction of the characteristic β-sheet content is preserved. As a major driving force, we identify the electrostatic interactions between Aβ charged side chains, including E22, D23, and K28, and lipid headgroups. Together with hydrogen bonding with atoms from lipid headgroups, these interactions can facilitate the penetration of hydrophobic C-terminal amino acids through the lipid headgroup region, which can finally lead both to further loss of the initial fibril structure and to local membrane-thinning effects. Our results may guide new experiments that could test the extent to which the structural features of water-formed amyloid fibrils are preserved, lost, or reshaped by membrane-mediated interactions.

Multiple Replica Repulsion Technique for Efficient Conformational Sampling of Biological Systems

Here, we propose a technique for sampling complex molecular systems with many degrees of freedom. The technique, termed “multiple replica repulsion” (MRR), does not suffer from poor scaling with the number of degrees of freedom associated with common replica exchange procedures and does not require sampling at high temperatures. The algorithm involves creation of multiple copies (replicas) of the system, which interact with one another through a repulsive potential that can be applied to the system as a whole or to portions of it. The proposed scheme prevents oversampling of the most populated states and provides accurate descriptions of conformational perturbations typically associated with sampling ground-state energy wells. The performance of MRR is illustrated for three systems of increasing complexity. A two-dimensional toy potential surface is used to probe the sampling efficiency as a function of key parameters of the procedure. MRR simulations of the Met-enkephalin pentapeptide, and the 76-residue protein ubiquitin, performed in presence of explicit water molecules and totaling 32 ns each, investigate the ability of MRR to characterize the conformational landscape of the peptide, and the protein native basin, respectively. Results obtained for the enkephalin peptide reflect more closely the extensive conformational flexibility of this peptide than previously reported simulations. Those obtained for ubiquitin show that conformational ensembles sampled by MRR largely encompass structural fluctuations relevant to biological recognition, which occur on the microsecond timescale, or are observed in crystal structures of ubiquitin complexes with other proteins. MRR thus emerges as a very promising simple and versatile technique for modeling the structural plasticity of complex biological systems.

Solvent Dielectric Effect and Side Chain Mutation on the Structural Stability of Burkholderia cepacia Lipase Active Site: A Quantum Mechanical/Molecular Mechanics Study

Quantum mechanical and molecular dynamics methods were used to analyze the structure and stability of neutral and zwitterionic configurations of the extracted active site sequence from a Burkholderia cepacia lipase, histidyl-seryl-glutamin (His86-Ser87-Gln88) and its mutated form, histidyl-cysteyl-glutamin (His86-Cys87-Gln88) in vacuum and different solvents. The effects of solvent dielectric constant, explicit and implicit water molecules and side chain mutation on the structure and stability of this sequence in both neutral and zwitterionic forms are represented. The quantum mechanics computations represent that the relative stability of zwitterionic and neutral configurations depends on the solvent structure and its dielectric constant. Therefore, in vacuum and the considered non-polar solvents, the neutral form of the interested sequences is more stable than the zwitterionic form, while their zwitterionic form is more stable than the neutral form in the aqueous solution and the investigated polar solvents in most cases. However, on the potential energy surfaces calculated, there is a barrier to proton transfer from the positively charged ammonium group to the negatively charged carboxylat group or from the ammonium group to the adjacent carbonyl oxygen and or from side chain oxygen and sulfur to negatively charged carboxylat group. Molecular dynamics simulations (MD) were also performed by using periodic boundary conditions for the zwitterionic configuration of the hydrated molecules in a box of water molecules. The obtained results demonstrated that the presence of explicit water molecules provides the more compact structures of the studied molecules. These simulations also indicated that side chain mutation and replacement of sulfur with oxygen leads to reduction of molecular flexibility and packing.

Avoiding gas-phase calculations in theoretical pK a predictions

CBS-QB3, two simplified and less computationally demanding versions of CBS-QB3, DFT-B3LYP, and HF quantum chemistry methods have been used in conjunction with the CPCM continuum solvent model to calculate the free energies of proton exchange reactions in water solution following an isodesmic reaction approach. According to our results, the precision of the predicted pK a values when compared to experiment is equivalent to that of the thermodynamic cycles that combine gas-phase and solution-phase calculations. However, in the aqueous isodesmic reaction schema, the accuracy of the results is less sensitive to the presence of explicit water molecules and to the global charges of the involved species since the free energies of solvation are not required. In addition, this procedure makes easier the prediction of pK a values for molecules that undergo large conformational changes in solvation process and makes possible the pK a prediction of unstable species in gas-phase such as some zwitterionic tautomers. The successive pK a values of few amino acids corresponding to the ionization of the α-carboxylic acid and α-amine groups, which is one of the problematic cases for thermodynamic cycles, were successfully calculated by employing the aqueous isodesmic reaction yielding mean absolute deviations of 0.22 and 0.19 pK a units for the first and second ionization processes, respectively.

Molecular dynamics and quantum chemical studies on incremental solvation of glycine

The conformational analysis of Glycine (Gly) amino acid in the presence of explicit water molecules is done using Molecular Dynamics (MD) simulation for over 10 ns time scale with step of 2 fs. Based on the hydrogen bond interactions, the solvated states of Gly and their distribution functions have been analyzed to identify the number of water molecules which fall within the first and second solvation shells. The ab initio and density functional theory (DFT) methods have been used to study the incremental solvation effect on Gly in gas phase with one to nine water molecules by constructing a hydration shell around Gly. Molecular geometries and energetical parameters of Gly⋯(W) n n = 1–9 complexes were studied by MP2, B3LYP and B3PW91 methods using 6-311G (2d, 2p) basis set. The interaction energies with BSSE corrections and the strength of the hydrogen bonds have been analyzed. The chemical hardness at HF/6-311G (2d, 2p) level of theory has been calculated for all the optimized structures. The topological analysis has been carried out for the water interacting complexes using Bader’s atoms in molecule (AIM) theory. The charge transfer from the proton acceptor to the anti-bonding orbital of proton donor in Gly⋯(W) n n = 1–9 complexes has been analyzed through Natural bond orbital (NBO) analysis. NMR calculations have been carried out on the basis of Cheeseman coworkers method at B3LYP/6-311G (2d, 2p) level of theory to analyse the molecular environment as well as the delocalization activities of electron cloud.

Comparative study of the hydrolysis of a third- and a first-generation platinum anticancer complexes

The hydrolysis of cis-[Pt(NH3)2Cl2] (cisplatin) and of the third-generation platinum anticancer compound (cis-[PtCl2(NH3)-(2-picoline)] (picoplatin) has been studied quantum-mechanically using density functional theory (mPW1PW91). Due to its asymmetry, picoplatin is an interesting case, since hydrolysis may proceed through two distinct reaction paths and with the entering water molecule sin or anti to the methyl group of 2-picoline. Solvent effects were taken into account either by applying the polarizable continuum model (PCM) solvent approach or by introducing a cluster of water molecules solvating the complex. With the PCM approach, it emerges that the steric hindrance of 2-picoline has a minimum impact on the activation barriers for picoplatin hydrolysis, since the water molecule approach is far from being axial and far from the methyl group. Accordingly, the TS state geometry with 5-coordinated platinum is not significantly more distorted than in the cisplatin case. Our results point out that the use of separated reactants as reference for energy barrier gives satisfactory results for each compound and produces correct relative magnitudes of first and second hydrolysis rate constants for each compound. However, this model is not able to predict the generally faster hydrolysis experimentally observed for cisplatin with respect to picoplatin. The study of the first hydrolysis step for the two compounds in the presence of explicit water molecules shows that the entering water molecule is strongly interacting with the others through a complex hydrogen bond network. The discrete solvation model is able to correctly predict a slightly slower hydrolysis of picoplatin highlighting the need of explicit solvation to predict small differences (within an order of magnitude) in the observed rate constants.

Understanding selectivity of hard and soft metal cations within biological systems using the subvalence concept. I. Application to blood coagulation: direct cation-protein electronic effects vs. indirect interactions through water networks.

Following a previous study by de Courcy et al. ((2009) Interdiscip. Sci. Comput. Life Sci. 1, 55-60), we demonstrate in this contribution, using quantum chemistry, that metal cations exhibit a specific topological signature in the electron localization of their density interacting with ligands according to its "soft" or "hard" character. Introducing the concept of metal cation subvalence, we show that a metal cation can split its outer-shell density (the so-called subvalent domains or basins) according to it capability to form a partly covalent bond involving charge transfer. Such behaviour is investigated by means of several quantum chemical interpretative methods encompasing the topological analysis of the Electron Localization Function (ELF) and Bader's Quantum Theory of Atoms in Molecules (QTAIM) and two energy decomposition analyses (EDA), namely the Restricted Variational Space (RVS) and Constrained Space Orbital Variations (CSOV) approaches. Further rationalization is performed by computing ELF and QTAIM local properties such as electrostatic distributed moments and local chemical descriptors such as condensed Fukui Functions and dual descriptors. These reactivity indexes are computed within the ELF topological analysis in addition to QTAIM offering access to non atomic reactivity local index, for example on lone pairs. We apply this "subvalence" concept to study the cation selectivity in enzymes involved in blood coagulation (GLA domains of three coagulation factors). We show that the calcium ions are clearly able to form partially covalent charge transfer networks between the subdomain of the metal ion and the carboxylate oxygen lone pairs whereas magnesium does not have such ability. Our analysis also explains the different role of two groups (high affinity and low affinity cation binding sites) present in GLA domains. If the presence of Ca(II) is mandatory in the central "high affinity" region to conserve a proper folding and a charge transfer network, external sites are better stabilised by Mg(II), rather than Ca(II), in agreement with experiment. The central role of discrete water molecules is also discussed in order to understand the stabilities of the observed X-rays structures of the Gla domain. Indeed, the presence of explicit water molecules generating indirect cation-protein interactions through water networks is shown to be able to reverse the observed electronic selectivity occuring when cations directly interact with the Gla domain without the need of water.

The catalytic effect of water on the keto–enol tautomerism. Pyruvate and acetylacetone: a computational challenge

The catalytic effect of explicit water molecules on the keto-enol tautomerism in a system of biological interest (enolpyruvate) has been investigated at the B3LYP/6-31++G** level by exploring the potential energy surface in the presence of 1 or 2 water molecules and comparing the energy profiles to the direct tautomerisation one. The water-assisted mechanisms turned out to be more favourable than the direct ones, in agreement with what occurred for the acetylacetone tautomerism in the presence of a single water molecule. To compare the behaviour of water in pyruvate and in acetylacetone, the two-water-assisted mechanism has been also examined for the latter at the B3LYP/6-31G* level. A number of stationary points for both compounds in vacuo and in the presence of explicit water molecules have been computed with DFT coupled to larger basis sets and at the MP2 level. Two diketo forms more stable than any of the keto-enol tautomers have been located, while for pyruvate the keto form is always more favourable than the enol one. The equilibrium constant for acetylacetone tautomerisation has been computed with high accuracy, performing a complete basis set extrapolation for the relative internal energy, to determine whether the quality of the method/basis set is responsible for the earlier modest agreement with the experimental value. Monte Carlo and molecular dynamics simulations helped characterize the solution structure and association features in the 0.03-0.22 molar concentration range.

A molecular simulation study of methylated and hydroxyl sugar-based self-assembled monolayers: Surface hydration and resistance to protein adsorption

In this work molecular simulations are performed to investigate protein interactions with hydroxylated and methylated mannitol and sorbitol terminated self-assembled monolayer (SAM) surfaces in the presence of explicit water molecules. The role of surface hydrogen bond donor versus acceptor groups is evaluated by comparing the hydration layer structure and resulting forces generated by the two classes of sugar SAM surfaces. Both hydroxyl and methyl-terminated sugar SAM surfaces interact with hydrating water molecules. Regardless of hydrogen bond donor or acceptor groups, both classes of sugar SAM surface groups interact strongly with hydrating water molecules to induce significant repulsive forces and resistance to protein adsorption. Our results indicate that the repulsive force generated on the probe protein is related to the ability of the surface to orient the hydration layer water. The repulsive force is also proportional to the number of hydrating water molecules interacting with the protein. The repulsive force and subsequent resistance to protein adsorption are dependent on the surface hydration, not the origin of that hydration.

Molecular Simulation Studies of Protein Interactions with Zwitterionic Phosphorylcholine Self-Assembled Monolayers in the Presence of Water

Molecular simulations were performed to study the interactions between a protein (lysozyme, LYZ) and phosphorylcholine-terminated self-assembled monolayers (PC-SAMs) in the presence of explicit water molecules and ions. The results show that the water molecules above the PC-SAM surface create a strong repulsive force on the protein as it approaches the surface. The structural and dynamic properties of the water molecules above the PC-SAM surface were analyzed to provide information regarding the role of hydration in surface resistance to protein adsorption. It can be seen from residence time dynamics that the water molecules immediately above the PC-SAM surface are significantly slowed down as compared to bulk water, suggesting that the PC-SAM surface generates a tightly bound, structured water layer around its head groups. Moreover, the orientational distribution and reorientational dynamics of the interfacial water molecules near the PC-SAM surface were found to have the ionic solvation nature of the PC head groups. These properties were also compared to those obtained previously for an oligo(ethylene glycol) (OEG) SAM system and bulk water.