Gibbs Free Energy Of Binding Research Articles

Vanadium doped 1T MoS2 nanosheets for highly efficient electrocatalytic hydrogen evolution in both acidic and alkaline solutions

Electrocatalysis plays a major role in the development of clean and sustainable energies. For efficient hydrogen evolution reaction (HER) in water splitting, active, robust, and cost-effective catalysts are highly desired. Here, we present a facile approach to fabricate 1T-phase dominant V-doped MoS2 nanosheets which can be easily grown on carbon paper at a large scale. The 5 at.% V-doped MoS2 nanosheets achieve excellent catalytic performance, showing more than 10-fold increase of current density compared with 2H MoS2 and a surprisingly low onset potential of 102 mV vs reversible hydrogen electrode (RHE). Moreover, it exhibits good catalytical stability in both acidic and alkaline solutions. The remarkable HER performance mainly attributes to the synergistic effects of the modified structure of MoS2 with enhanced active sites, increased electrical conductivity, optimised energy level and near-zero Gibbs free energy of hydrogen binding. This work may shed light on achieving highly efficient electrocatalysts toward practical applications.

Magneto-electronic property in zigzag phosphorene nanoribbons doped with transition metal atom

The magneto-electronic properties of zigzag phosphorene nanoribbons (ZPNRs) doped, respectively, with iron (Fe), cobalt (Co) and nickel (Ni) atoms are investigated by the first-principles method based on density functional theory. The calculated results show that the structures of doped and undoped ZPNR are stable because their binding energy and Gibbs free energy are negative, and the Forcite annealing dynamics simulation shows that the thermal stabilities of all doped ZPNRs are extremely high. The ground states of pristine ZPNRs and ZPNRs doped with Co atoms are nonmagnetic states, while the ground states of ZPNRs doped with Fe or Ni atoms are ferromagnetic states. When they are in the nonmagnetic states, the pristine ZPNRs and ZPNRs doped with Co atoms turn into semiconductors, while the ZPNRs doped with Fe or Ni atoms become metals. The undoped ZPNRs are direct band gap semiconductors, while the ZPNRs doped with Co atoms are indirect band gap semiconductors, and the band gaps of the latter are smaller than those of the former. The changes of the properties of the ZPNRs are due to the introduction of impurity energy band into the energy band structures. The spin-polarized calculation displays that the pristine ZPNRs and ZPNRs doped with Co atoms are non-magnetic, and the ZPNRs doped with Fe or Ni atoms are magnetic but only in the ferromagnetic state. In the ferromagnetic state, the ZPNRs doped with Fe atoms are spin semiconductors, while the ZPNR doped with Ni atoms are spin half-metals. This means that the half-metal feature can be realized by doping Ni atom into ZPNR. The magnetism of ZPNRs doped with Fe or Ni atoms is mainly contributed by impurity atoms, and the occurrence of magnetism is due to the existence of unpaired electrons in ZPNR. The doping position has a certain influence on the electromagnetic properties of ZPNR. In the ferromagnetic state, the ZPNRs are half-metals when the Ni atoms are doped near the edge of the nanoribbons, while the ZPNRs are spin semiconductors as the Ni atoms are doped near the symmetric center of the nanoribbons. These results might be of significance for developing the phosphorene based electronic nanodevices

Social distance teaching and learning: An online DNA nucleotide binding lab experience for health sciences and non-major students.

DNA analysis is a common diagnostic tool in healthcare: ranging from microbial typing (e.g. DNA strands of viral, bacterial and even fungal pathogens), oncological screen (e.g. Breast cancer detection via DNA analysis of any BRCA gene mutations), genetic amniocentesis test (a medical technique used in determining chromosomal conditions such as down syndrome in the fetus) and a host of other medical diagnostics based on the knowledge of deoxyribonucleic acid (DNA) and the genetic information carried in this macromolecule. However, such a wide-range of medical diagnostic mechanisms using DNA begs the question: How much does the undergraduate health sciences and/or non-major students understand about the basic biochemical properties of DNA? Here, a virtual lab module was used (with the addition of Pre and Post Lab Questions and a Discussion Topic relating DNA to Healthcare) along with a learning management system, to help undergraduate health sciences students visualize the biochemical properties of DNA molecule, such as binding constant and Gibbs free energy of binding. This lab was adapted to offer a platform on which an Instructor can design steps for students to explore the DNA nucleotide binding module during a time in which social distance curricula is necessary.

Gated Resonance Energy Transfer (gRET) Controlled by Programmed Death Protein Ligand 1.

The resonance energy transfer (RET) between an excited fluorescent probe molecule and a plasmonic nanoparticle (AuNP) has been investigated to evaluate the effect of protein molecules on the RET efficiency. We have found that the energy transfer to a functionalized AuNP can be modulated by a sub-monolayer film of programmed death-ligand 1 (PD-L1) protein. The interactions of PD-L1 with AuNP@Cit involve incorporation of the protein in AuNP shell and formation of a submonolayer adsorption film with voids enabling gated surface plasmon resonance energy transfer (SPRET). A model of the gated-RET system based on the protein size, estimated using Fisher–Polikarpov–Craievich density approximation, has been developed and can be utilized for other proteins, with minimum data requirement, as well. The value of the equilibrium constant KL determined for the Langmuir isotherm is high: KL = 1.27 × 108 M−1, enabling highly sensitive control of the gated-RET by PD-L1. Thus, with the gated-RET technique, one can determine PD-L1 within the dynamic range, extending from 1.2 to 50 nM. Moreover, we have found that the Gibbs free energy for PD-L1 binding to AuNP@Cit is −46.26 kJ/mol (−11.05 kcal/mol), indicating a strong adsorption with supramolecular interactions. The proposed gated-RET system, with the fluorescence intensity of the fluorophore probe molecule modulated by plasmonic quenching with AuNP and shielding of energy transfer by the adsorbed PD-L1 can be further developed for determination of PD-L1 in pharmaceutical formulations for immune checkpoint control in cancer therapy.

Binding of Organophosphorus Nerve Agents and Their Simulants to Metal Salts.

Nerve agents (NAs) pose a great threat to society because they are easy to produce and are deadly in nature, which makes developing methods to detect, adsorb, and destroy them crucial. To enable the development of these methods, we report the use of first principles electronic structure calculations to understand the binding properties of NAs and NA simulants on metal salt surfaces. We report calculated Gibbs free binding energies (GBE) for four NAs (tabun (GA), sarin (GB), soman (GD), and venomous X (VX)) and five NA simulants (dimethyl methylphosphonate (DMMP), dimethyl chlorophosphate (DMCP), trimethyl phosphate (TMP), methyl dichlorophosphate (MDCP), and di-isopropyl methylphosphonate (DIMP)) on metal perchlorate and metal nitrate salts using density functional theory. Our results indicate a general trend in the binding strength of NAs and NA simulants to metal salt surfaces: MDCP < DMCP < GA < GD ≈ GB < TMP < VX ≈ DMMP < DIMP. Based on their binding properties on salt surfaces, we identify the most effective simulant for each of the studied NAs as follows: DMCP for GA, TMP for GB and GD, and DMMP for VX. To illustrate the utility of the binding energies calculated in our study, we address the design of NA sensors based on the competitive binding of NAs and liquid crystalline compounds on metal salts. We compare our results with previous experimental findings and provide a list of promising combinations of liquid crystal and metal salt systems to selectively and sensitively detect NAs. Our study highlights the great value of computational chemistry for designing selective and sensitive NA sensors while minimizing the number of very dangerous experiments involving NAs.

Investigation of Physicochemical Properties of Aggregated Models of [MIM+]2[C(CN)3-]2 Ionic Liquid: A Theoretical Study

In present work, the aggregation behavior of ion-pairs in [MIM+]2[C(CN)3-]2 ionic liquid was investigated. The quantum chemical calculations were carried out to determine the structural parameters, interaction energies, hydrogen bonding, physical and topological properties of the clusters formed in the ionic liquid of [MIM+]2[C(CN)3-]2. The solvent effect on the stability of clusters was examined. The Gibbs free energy of solvation and the Gibbs free binding energy of clusters in various solvents were calculated. The results show that with decreasing the polarity of the solvent, the tendency to the formation of aggregate increases. Also, the solvation energies of the clusters increase with decreasing the solvent's dielectric constant. The NBO analysis was performed to evaluate the charge transfer in complexes. The AIM analysis was performed in order to characterize intermolecular interactions.

Virtual Screening Based on Pharmacophore to Discover Host ER Alpha-Glucosidase II Inhibitor for Dengue Therapy

Dengue is one of the crucial diseases in human-caused by dengue virus (DENV) infection. However, the development of DENV antiviral is often facing a problem because no effective drug to treat infection caused by all DENV serotypes. The inhibition of host protein involved in DENV life cycle can be a potential approach in dengue drug discovery, and also avoiding antiviral resistance. Endoplasmic Reticulum (ER) α-glucosidase II is one of the target host protein in DENV endoplasmic reticulum that plays an important role in the maturation process of DENV envelope glycoprotein. Natural products have been known as an essential source of a lead compound for drug discovery due to their therapeutic potency. In this research, pharmacophore-based virtual screening and molecular docking simulations were performed to find ligand that has potential to inhibit α-glucosidase II activity. About 67,609 natural products from InterBioScreen (IBS) database were used in the simulation as ligands with α-glucosidase II as the protein target. After subjected to Lipinski’s Rule of Five, druglikeness, nasty functions, and toxicity screening using DataWarrior software, 17,462 ligands were obtained. The pharmacophore features for molecular docking simulation was obtained from Protein-Ligand Interaction Fingerprint (PLIF) analysis using eight α-glucosidase II protein with different ligands. Based on virtual screening, rigid, and flexible docking simulations using Molecular Operating Environment (MOE) software, 32 ligands have lower Gibbs free binding energy (ΔGbinding) compared to the standards. Two best ligands, namely STOCK1N-85545 and STOCK1N-86400 which belong alkaloid derivatives, showed the exceptional ligand interaction and had the lowest ΔGbinding of-11.204 and-10.276 kcal/mol, respectively. The ligands were identified to have a binding interaction with amino acid Asp564 and Asp640 in α-glucosidase II catalytic site. STOCK1N-85545 and STOCK1N-86400 were also identified to have a good pharmacological properties after subjected to ADME-tox test using Toxtree, SwissADME, admetSAR, and pkCSM software.

Efficient Electronic Structure to Stabilize N2‐Bridged Dinuclear Complexes Intended for N2 Activation: Iminophosphorane Iron(I) and Cobalt(I)

We examined the stability of the N2‐ligated mononuclear and N2‐bridged dinuclear complexes for FeI and CoI with the tridentate iminophosphorane ligand, which are in potentially deactivated state for catalytic N2 fixation processes, using density functional theory (DFT) method. The calculated Gibbs free energies of the N2 binding and N2‐bridge formation reactions show that the N2‐bridged FeI‐dinuclear complex is more favorable than the N2 FeI‐mononuclear complex in contrast to the CoI‐mononuclear complexes, which is only the available complex, even if at –80 °C. The stability of the N2‐bridged dinuclear metal complexes has a close relation to the M–N2 bond strength ruled by occupation of the pairs of dπu orbitals, in which the ungerade couples of the dπ orbitals interact with the occupied π orbitals of N2 in antibonding manner. For the catalytic activity of FeI mononuclear complexes, the appropriate order of orbitals to occupy the dπu orbitals is necessary, which is produced by the T‐shaped coordination geometry the ancillary ligands construct.

Analyses of Ligand Binding to IP3 Receptors Using Fluorescence Polarization.

Fluorescence polarization (FP) can be used to measure binding of a small fluorescent ligand to a larger protein because the ligand rotates more rapidly in its free form than when bound. When excited with plane polarized light, the free fluorescent ligand emits depolarized light, which can be quantified. Upon binding, its rotation is reduced and more of the emitted light remains polarized. This allows FP to be used as a nondestructive assay of ligand binding. Here we describe a fast, high-throughput FP assay to quantify the binding of fluorescently labeled inositol 1,4,5-trisphosphate (IP3) to N-terminal fragments of the IP3 receptor. The assay is fast (1-6h), it avoids use of radioactive materials and when measurements are performed at different temperatures, it can resolve Gibbs free energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°) changes of ligand binding.

Screening of Anti-mycobacterial Phytochemical Compounds for Potential Inhibitors against Mycobacterium Tuberculosis Isocitrate Lyase.

Virtual screening, molecular docking and MD simulation study has been integrated for screening of phytochemical based anti-mycobacterial compounds. Docking study of reported MtbICL inhibitors has shown an average binding affinity score -7.30 Kcal/mol. In virtual screening, compounds exhibiting lower binding energy than calculated average binding energy were selected as top hit compounds followed by calculation of drug likeness property. Relationship between experimental IC50 value and calculated binding gibbs free energy of reported inhibitors was also calculated through regression analysis to predict IC50 value of potential inhibitors. Docking and MD simulation studies of top hit compounds have identified shinjudilactone (quassinoid), lecheronol A (pimarane) and caniojane (diterpene) as potential MtbICL inhibitors. Phytochemical based anti-mycobacterial compound can further developed into effective drugs against persistence tuberculosis with lesser toxicity and side effects.

Thermodynamic examination of magnesium ion binding in the M‐box core 2 4×4 internal loop

RNA binds to magnesium ions through diffuse and site‐specific interactions. Diffuse binding of magnesium ions to the backbone occurs in all RNA and is critical for the stabilization of RNA structure. Magnesium ions also bind to specific sites in particular RNA structures, often with direct Mg2+‐RNA bond formation. In this study, Isothermal Titration Calorimetry (ITC) was used to experimentally measure the enthalpy, binding constants, and Gibbs free energy of diffuse and site‐specific binding of magnesium ions to the core 2 of the Salmonella Typhimurium M‐box riboswitch. This Mg2+ binding bacterial riboswitch upregulates magnesium transporting proteins when intracellular ion concentrations are above an acceptable level. Crystal structure of the M‐box riboswitch RNA shows eight magnesium ion binding sites clustered in three cores. The core 2 of the M‐box riboswitch is made up of a 4×4 adenine‐rich internal loop that binds magnesium ions at residues A63 and A80. RNA constructs were designed to mimic the wild type core 2 and were also modified at positions A63 and A80. A helix construct, with the internal loop deleted, was also utilized. A statistical model for RNA‐Mg2+ binding was used to fit the ITC data to determine the thermodynamic parameters of diffuse and site‐specific magnesium ion binding to the RNA. The models used to fit ITC for ion binding will be presented. In general, we find that the diffuse binding is spontaneous, endothermic and entropically driven with binding constants in the low millimolar range. Site‐specific binding showed micromolar binding constants.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pharmacophore-based virtual screening and molecular docking simulation of terpenoid compounds as the inhibitor of sonic hedgehog protein for colorectal cancer therapy

Colorectal cancer remains as the global health burden, which accounts for roughly 1 - 2 million new cases and 600,000 deaths per year. Hedgehog (Hh) signalling pathway has an imperative role in the mechanism and formation of colorectal cancer. Sonic hedgehog (Shh) protein is the most studied Hh protein because it is expressed by several tissues and experiments with Shh protein are generally applicable to other Hh homologs. In the present study, about 56,336 terpenoid compounds were screened through various computational methods using pharmacophore-based virtual screening and molecular docking simulation to determine their inhibitory potency against Shh protein. From molecular docking simulation results, about ten ligands have been selected according to their Gibbs free binding energies ΔGbinding) and the molecular interactions that formed during the formation of the terpenoid compound-Shh complex. Three terpenoid compounds, namely arganine J, asiaticoside A, and clinoposide A, shown a very high binding affinity toward Shh protein due to their lower ΔGbinding than robotnikinin, the standard ligand. Moreover, ADME-Tox, bioactivity, bioavailability, and pharmacology test results revealed that these compounds have better biological and pharmacological activity than the other terpenoid compounds. For further research, these terpenoid compounds can be used as a drug candidate for colorectal cancer therapy.

Virtual screening of natural products as an inhibitor of DNA methyltransferase 1 enzyme for breast cancer disease

Breast cancer is the most prevalent cancer in woman worldwide. It has the highest number of new cases which amounted to 40 per 100,000 cases per year, 12.9% of which leads to death. Epigenetic alteration plays a vital role in the process of cancer cell formation and propagation. DNA methylation is one of the most common types of epigenetic alteration which generally leads to breast cancer. The DNA Methylation, a transfer of methyl group from S-adenosyl-methionine (SAM) to cytosine in the CpG dinucleotide, is catalysed by a DNA Methyltransferase-1 (DNMT1) enzyme. In the present study, we performed a virtual screening of natural product compounds as an inhibitor of the DNMT1 enzyme. Virtual screening was conducted on 26,731 natural products obtained from the NCBI PubChem database. Three steps of rigid and one step of flexible molecular docking simulations were performed using MOE 2014.09. Through the simulations, 10 best ligands based on the Gibbs free binding energies ΔGbinding) and the ligand-enzyme complex interactions were identified. The pharmacological test was conducted to observe the physicochemical, toxicity, carcinogenicity-mutagenicity, and bioactivity properties by employing DataWarrior 4.7.2., Toxtree, Molinspiration, admetSAR, and SWISSADME software. The results revealed that three best ligands from the phenolic group were selected due to their exceptional pharmacological characteristics as the drug candidate for breast cancer therapy.

Discovery of biogenic-based compound as potential heat-shock protein 90 inhibitor through fragment-based drug design

Ebola virus (EBOV) is a negative-sense RNA virus that belongs to Filoviridae family which recognized as one of the deadliest virus that can cause severe haemorrhagic fever. Recent studies have shown that heat-shock protein 90 (Hsp90), an essential molecular chaperone, plays an imperative role in the replication of EBOV. In the present study, about 112,113 biogenic compounds from ZINC15 database were screened through computational study through Rule of Three, druglikeness, and toxicity screening, followed by molecular docking simulation to determine the potential biogenic-based compound as lead compounds. These compounds were later linked by each other to generate a novel compound for inhibiting Hsp90 protein. Throughout this study, about 742 fragments were obtained through the first screening process, while the first docking simulation produced 452 lead fragments. After the linking processes were conducted, about 81 compounds were produced through the second docking simulation. Furthermore, the docking simulation also revealed that HAI_77 gave the best ligand interaction and had the lowest Gibbs free binding energy at -14.157 kcal/mol. Thus, HAI_77 ligand can be proposed as novel drug candidates for the EBOV therapeutics targeting Hsp90 ligand.

An oncoinformatics study to predict the inhibitory potential of recent FDA-approved anti-cancer drugs against human Polo-like kinase 1 enzyme: a step towards dual-target cancer medication.

Cancer prevalence has increased at an alarming rate worldwide. Complexity, resistance mechanism and multiple compensatory survival pathways of cancer cells have abated the response of currently available cancer medications. Therefore, multi-target agents rather than single target might provide a better solution to these cancer therapy issues. In the present study, anti-PLK1 (Polo-like kinase 1) potential of the eight FDA-approved (2017) anti-cancer drugs have been explored using molecular docking approach. Out of all the tested drugs, brigatinib, niraparib and ribociclib showed better binding affinity towards the 'kinase domain' of PLK1. The Gibbs free binding energy (ΔG) and inhibition constant (K i) values for brigatinib, niraparib and ribociclib interaction with the kinase domain of PLK1 were '- 8.05kcal/mol and 1.26µM', '- 8.35kcal/mol and 0.729µM' and '- 7.29kcal/mol and 4.52µM', respectively. Interestingly, the docking results of these three drugs were better than the known PLK1 inhibitors (BI-2536 and rigosertib). The ΔG and K i values for BI-2536 and rigosertib interaction with the kinase domain of PLK1 were '- 6.8kcal/mol and 10.38µM' and '- 6.6kcal/mol and 14.51µM', respectively. Brigatinib, niraparib and ribociclib have been approved by FDA for the treatment of non-small cell lung cancer, ovarian/fallopian tube cancer and breast cancer, respectively. PLK1 is regarded as a potential cancer target, and it is specifically over-expressed in different types of cancer cells, including aforementioned cancers. Actually, the target enzymes for anti-cancer action of brigatinib, niraparib and ribociclib are tyrosine kinase, poly(ADP-ribose) polymerase and cyclin-dependent kinase 4/6, respectively. However, based on our outcomes, we could safely state that PLK1 might plausibly emerge as an add-on target for each of these three anti-cancer drugs. We strongly believe that this study would assist in the development of better dual-targeting cancer therapeutic agent in the near future.

Determination of Ligand Binding Affinity and Specificity of Purified START Domains by Thermal Shift Assays Using Circular Dichroism.

The use of direct calorimetric methods such as isothermal titration calorimetry for measuring the affinity and specificity of protein-ligand interactions requires large amounts of proteins and ligands. When material is scarce and/or in the absence of calorimeters, thermal Shift Assays (TSA) using Circular Dichroism (CD) or other spectroscopic methods offers an alternative and quantitative method for the determination of apparent or indirect thermodynamical parameters describing the affinity of ligands for proteins. Indeed, the binding constants of ligands (Kb) and other parameters such as the enthalpy and Gibbs free energy of binding may be estimated from the changes in the stability curves ΔGu(T) of a protein in the presence of a ligand. Here we describe the application of two different procedures proposed by Layton and Hellinga et al. (Biochemistry 49:10831-10841, 2010) to evaluate the apparent Kb of testosterone to the START (StAR-related lipid transfer domain) domains.

Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D↑G↑S mutant in the South African HIV-1 subtype C protease

Herein, we report the effect of nine FDA approved protease inhibitor drugs against a new HIV-1 subtype C mutant protease, E35D↑G↑S. The mutant has five mutations, E35D, two insertions, position 36 (G and S), and D60E. Kinetics, inhibition constants, vitality, Gibbs free binding energies are reported. The variant showed a decreased affinity for substrate and low catalytic efficiency compared to the wild type. There was a significant decrease in the binding of seven FDA approved protease inhibitors against the mutant (p < .0001). Amprenavir and ritonavir showed the least decrease, but still significant reduced activity in comparison to the wildtype (4 and 5 folds, respectively, p = .0021 and .003, respectively). Nelfinavir and atazanavir were the worst inhibitors against the variant as seen from the IC50, with values of 1401 ± 3.0 and 685 ± 3.0 nM, respectively. Thermodynamics data showed less favourable Gibbs free binding energies for the protease inhibitors to the mutant.

A theoretical investigation on the structures of (NH3)·(H2SO4)·(H2O)0‐14 clusters

AbstractTernary clusters (NH3)·(H2SO4)·(H2O)n have been widely studied. However, the structures and binding energies of relatively larger cluster (n &gt; 6) remain unclear, which hinders the study of other interesting properties. Ternary clusters of (NH3)·(H2SO4)·(H2O)n, n = 0‐14, were investigated using MD simulations and quantum chemical calculations. For n = 1, a proton was transferred from H2SO4 to NH3. For n = 10, both protons of H2SO4 were transferred to NH3 and H2O, respectively. The NH4+ and HSO4− formed a contact ion‐pair [NH4+‐HSO4−] for n = 1‐6 and a solvent separated ion‐pair [NH4+‐H2O‐HSO4−] for n = 7‐9. Therefore, we observed two obvious transitions from neutral to single protonation (from H2SO4 to NH3) to double protonation (from H2SO4 to NH3 and H2O) with increasing n. In general, the structures with single protonation and solvated ion‐pair were higher in entropy than those with double protonation and contact ion‐pair of single protonation and were thus preferred at higher temperature. As a result, the inversion between single and double protonated clusters was postponed until n = 12 according to the average binding Gibbs free energy at the normal condition. These results can serve as a good start point for studies of the other properties of these clusters and as a model for the solvation of the [H2SO4‐NH3] complex in bulk water.

FRAGMENT-BASED LEAD COMPOUND DESIGN TO INHIBIT EBOLA VP35 THROUGH COMPUTATIONAL STUDIES

Ebola virus (EBOV) is a virus that is classified under Filoviridae family as a pathogenicorganism. On March 2016, World Health Organization (WHO) reported that 28.646 cases caused by EBOV. Thus, it is important to find the antiviral drug for this disease because it can create the epidemic around the world. EBOV VP35 is a potential drug target because it has the component of the viral RNA polymerase complex that will hamper the host interferon (IFN) production. In this research, about 6.662 fragments were obtained from ZINC15 Biogenic Database after the Rules of Three, and pharmacological properties parameters were applied. After that, these fragments were docked into the active side of EBOV VP35 using MOE 2014.09 software. The potential fragments from previous docking simulations were linked each other, resulting 91 ligands in the process. Furthermore, the docking simulation was conducted again anddiscovered the best three ligands that have lower Gibbs free binding energy than the standards. Moreover, the pharmacological prediction tests were also done to find the ligand with excellent molecular properties. The best three ligands from these tests were continued into molecular dynamics simulation. In the end, we conclude that the LEB 31 ligand can be the new drug candidate as EBOV VP35 inhibitor based on molecular docking, pharmacological prediction test, and molecular dynamic.

Interaction of Proteins with Polyelectrolytes: Comparison of Theory to Experiment.

We discuss recent investigations of the interaction of polyelectrolytes with proteins. In particular, we review our recent studies on the interaction of simple proteins such as human serum albumin (HSA) and lysozyme with linear polyelectrolytes, charged dendrimers, charged networks, and polyelectrolyte brushes. In all cases discussed here, we combined experimental work with molecular dynamics (MD) simulations and mean-field theories. In particular, isothermal titration calorimetry (ITC) has been employed to obtain the respective binding constants Kb and the Gibbs free energy of binding. MD simulations with explicit counterions but implicit water demonstrate that counterion release is the main driving force for the binding of proteins to strongly charged polyelectrolytes: patches of positive charges located on the surface of the protein become multivalent counterions of the polyelectrolyte, thereby releasing a number of counterions condensed on the polyelectrolyte. The binding Gibbs free energy due to counterion release is predicted to scale with the logarithm of the salt concentration in the system, which is verified by both simulations and experiment. In several cases, namely, for the interaction of proteins with linear polyelectrolytes and highly charged hydrophilic dendrimers, the binding constant could be calculated from simulations to very good approximation. This finding demonstrated that in these cases explicit hydration effects do not contribute to the Gibbs free energy of binding. The Gibbs free energy can also be used to predict the kinetics of protein uptake by microgels for a given system by applying dynamic density functional theory. The entire discussion demonstrates that the direct comparison of theory with experiments can lead to a full understanding of the interaction of proteins with charged polymers. Possible implications for applications, such as drug design, are discussed.