Assessing the performance of the MM/PBSA and MM/GBSA methods. 10. Impacts of enhanced sampling and variable dielectric model on protein–protein Interactions

Wang, Ercheng; Weng, Gaoqi; Sun, Huiyong; Du, Hongyan; Zhu, Feng; Fu, Chen; Wang, Zhe; Hou, Tingjun

doi:10.1039/c9cp04096j

Cited by 94 publications

(93 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It can be 1.0, 2.0 or 4.0 in different MM-PBSA calculations. [71][72][73][74] Insulin is an essential protein in treating the disease. Understanding the binding mechanism of insulin dimer will be useful to design drug.…”

Section: Resultsmentioning

confidence: 99%

Calculating the absolute binding free energy of the insulin dimer in an explicit solvent

Gong

Zhang

et al. 2020

RSC Adv.

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Calculating the absolute binding free energy of the insulin dimer in an explicit solvent

Gong

Zhang

et al. 2020

RSC Adv.

View full text Add to dashboard Cite

show abstract

“…On the other hand, the molecular mechanical force field (MMFF)-based scoring functions, are physical and more accurate, but much less efficient. With the ever increasing computer power, MMFF-based free energy calculation methods, such as the endpoint MM-PB/GBSA (molecular mechanics-Poisson Boltzmann/ Generalized Born Surface Area) methods 2,3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21] and the alchemical thermodynamic integration (TI) and free energy perturbation (FEP) methods, 22,23 have been extensively applied in structure-based drug discovery projects. Recently we've developed a hierarchical virtual screening (HVS)to balance the efficiency and accuracy and improve the success rate of rational drug design.…”

Section: Introductionmentioning

confidence: 99%

Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study

Wang

2020

Preprint

129

169

View full text Add to dashboard Cite

The recent outbreak of novel coronavirus disease -19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D-structures of key virous proteins are resolved. Taking the advantage of a recently released crystal structure of COVID-19 protease in complex with a covalently-bonded inhibitor, N3, 1 I conducted virtual docking screening of approved drugs and drug candidates in clinical trials.For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an endpoint method called MM-PBSA-WSAS. 2-4 Several promising known drugs stand out as potential inhibitors of COVID-19 protease, including Carfilzomib, Eravacycline, Valrubicin, Lopinavir and Elbasvir. Carfilzomib, an approved anti-cancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, -13.82 kcal/mol. Streptomycin, an antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (-3.82 kcal/mol) is not nearly as low as that of the neutral form (-7.92 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of -12.86 kcal/mol. Detailed receptor-ligand interactions were analyzed and hot spots for the receptor-ligand binding were identified. I found that one hotspot residue HIS41, is a conserved residue across many viruses including COVID-19, SARS, MERS, and HCV. The findings of this study can facilitate rational drug design targeting the COVID-19 protease.

show abstract

“…Different trajectories like root mean square deviation (RMSD), root mean square fluctuation (RMSF) and number of hydrogen bonds ware determined through MD simulations. (Duan et al, 2019;Skjevik et al, 2015;Srivastava & Sastry, 2012;Wang et al, 2019;Xu, Sun, Li, Wang, & Hou, 2013) The RMSD curve is obtained from correlating time with the deviations to understand the stability of the complexes in comparison of the protease alone and can be determined based on the following equation. (Alexandrescu, Snyder, & Abildgaard, 2001;Bruschweiler, 2003) Where N is the number of atoms, X m , Y m , Z m are the Cartesian coordinates of the initial structure and X l , Y l , Z l are the Cartesian coordinates of trajectory at frame t.…”

Section: Methodsmentioning

confidence: 99%

Promising Acyclovir and its derivatives to inhibit the protease of SARS-CoV-2: Molecular Docking and Molecular Dynamics simulations

Kumar

Kumari

Bahadur

et al. 2020

Preprint

View full text Add to dashboard Cite

Till date, more than 40 million people are affected throughout the world due to the COVID-19. Therefore, there is an urgency to find a solution to cure this infection. It is is due to the SARS-CoV-2 infection and the authors have targetted the protease of the SARS-CoV-2 so the infection will not spread. Herein, the authors have selected the antiviral drug, acyclovir for the inhibition of protease of the SARS-CoV-2. Acyclovir is a popular and selective antiherpes agent and started a new beginning for the viral infection. The other name of acyclovir is aciclovir and is being used in the treatment of chickenpox, and shingles. Further, it can be used in avoidance of cytomegalovirus infections. Even, acyclovir can used to cure the patients suffering from cold scores, shingles and also decreases the pain.In the present work, acyclovir (CMPD1) and its two derivatives, the first derivative is Ganciclovir (CMPD2) and the second derivative is (CMPD3). These three molecules were used to inhibit the protease of SARS-CoV-2. It was studied through the molecular docking, molecular dynamics simulations etc. Herein, simulations method were used to calculate relative change in binding free energy under the influence of Amber force field through MM-GBSA. The structural behavior of complex system with acyclovir and its derivatives were observed in term of RMSD and RMSF for all residues. Authors observed that complex of CMPD3 with the protease is stable and has less fluctuation than the native protease. Further, CMPD3 follow the creteria of all drug likeness term and it showed good activity against SARS-CoV-2. It was suggested that CMPD3 may be used as a inhibitor for coronavirus activity to protect life of human being in world.

show abstract

Assessing the performance of the MM/PBSA and MM/GBSA methods. 10. Impacts of enhanced sampling and variable dielectric model on protein–protein Interactions

Abstract: Enhanced sampling has been extensively used to capture the conformational transitions in protein folding, but it attracts much less attention in the studies of protein–protein recognition.

Cited by 94 publications

References 94 publications

Calculating the absolute binding free energy of the insulin dimer in an explicit solvent

Calculating the absolute binding free energy of the insulin dimer in an explicit solvent

Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study

Promising Acyclovir and its derivatives to inhibit the protease of SARS-CoV-2: Molecular Docking and Molecular Dynamics simulations

Contact Info

Product

Resources

About