Deciphering Cryptic Binding Sites on Proteins by Mixed-Solvent Molecular Dynamics

2017 ◽  
Vol 57 (6) ◽  
pp. 1388-1401 ◽  
Author(s):  
S. Roy Kimura ◽  
Hai Peng Hu ◽  
Anatoly M. Ruvinsky ◽  
Woody Sherman ◽  
Angelo D. Favia
Keyword(s):  
Molecular Dynamics ◽  
Binding Sites ◽  
Mixed Solvent ◽  
Cryptic Binding Sites

scholarly journals Investigating Cryptic Binding Sites by Molecular Dynamics Simulations

2020 ◽  
Vol 53 (3) ◽  
pp. 654-661 ◽  
Author(s):  
Antonija Kuzmanic ◽  
Gregory R. Bowman ◽  
Jordi Juarez-Jimenez ◽  
Julien Michel ◽  
Francesco L. Gervasio
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Sites ◽  
Cryptic Binding Sites ◽  
Dynamics Simulations

scholarly journals Study of Endogen Substrates, Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1051
Author(s):  
Edgardo Becerra ◽  
Giovanny Aguilera-Durán ◽  
Laura Berumen ◽  
Antonio Romo-Mancillas ◽  
Guadalupe García-Alcocer
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Binding Sites ◽  
Adenosine Monophosphate ◽  
Competitive Inhibitor ◽  
Umbrella Sampling ◽  
Coarse Grained ◽  
Nucleotide Polymorphisms

Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively). The results showed that the three MRP4 structures had significantly different conformations at given sites, leading to differences in the docking scores (DS) and binding sites of three different groups of molecules. Folic acid (FA) had the highest variation in DS on G187W concerning WT-MRP4. WT-MRP4, G187W, Y556C, and FA had different conformations through 25 ns AA-MD. Umbrella sampling simulations indicated that the Y556C-FA complex was the most stable one with or without ATP. In Y556C, the cyclic adenosine monophosphate (cAMP) and ceefourin-1 binding sites are located out of the entrance of the inner cavity, which suggests that both cAMP and ceefourin-1 may not be transported. The binding site for cAMP and ceefourin-1 is quite similar and the affinity (binding energy) of ceefourin-1 to WT-MRP4, G187W, and Y556C is greater than the affinity of cAMP, which may suggest that ceefourin-1 works as a competitive inhibitor. In conclusion, the nsSNPs G187W and Y556C lead to changes in protein conformation, which modifies the ligand binding site, DS, and binding energy.

scholarly journals Identifying binding hot spots on protein surfaces by mixed-solvent molecular dynamics: HIV-1 protease as a test case

Biopolymers ◽  
2015 ◽  
Vol 105 (1) ◽  
pp. 21-34 ◽  
Author(s):  
Peter M. U. Ung ◽  
Phani Ghanakota ◽  
Sarah E. Graham ◽  
Katrina W. Lexa ◽  
Heather A. Carlson
Keyword(s):  
Molecular Dynamics ◽  
Hot Spots ◽  
Mixed Solvent ◽  
Test Case ◽  
Protein Surfaces ◽  
Hiv 1

scholarly journals On the dynamics of some small structural motifs in rRNA upon ligand binding

2008 ◽  
Vol 73 (1) ◽  
pp. 41-53
Author(s):  
Aleksandra Rakic ◽  
Petar Mitrasinovic
Keyword(s):  
Molecular Dynamics ◽  
Conformational Changes ◽  
Binding Sites ◽  
De Novo ◽  
Reference Structure ◽  
Base Pairs ◽  
Rna Sequences ◽  
Conformational Model ◽  
Thermodynamic Variables ◽  
Dynamics Simulations

The present study characterizes using molecular dynamics simulations the behavior of the GAA (1186-1188) hairpin triloops with their closing c-g base pairs in large ribonucleoligand complexes (PDB IDs: 1njn, 1nwy, 1jzx). The relative energies of the motifs in the complexes with respect to that in the reference structure (unbound form of rRNA; PDB ID: 1njp) display the trends that agree with those of the conformational parameters reported in a previous study1 utilizing the de novo pseudotorsional (?,?) approach. The RNA regions around the actual RNA-ligand contacts, which experience the most substantial conformational changes upon formation of the complexes were identified. The thermodynamic parameters, based on a two-state conformational model of RNA sequences containing 15, 21 and 27 nucleotides in the immediate vicinity of the particular binding sites, were evaluated. From a more structural standpoint, the strain of a triloop, being far from the specific contacts and interacting primarily with other parts of the ribosome, was established as a structural feature which conforms to the trend of the average values of the thermodynamic variables corresponding to the three motifs defined by the 15-, 21- and 27-nucleotide sequences. From a more functional standpoint, RNA-ligand recognition is suggested to be presumably dictated by the types of ligands in the complexes.

Combining fragment homology modeling with molecular dynamics aims at prediction of Ca2+ binding sites in CaBPs

2013 ◽  
Vol 27 (8) ◽  
pp. 697-705 ◽  
Author(s):  
ChunLi Pang ◽  
TianGuang Cao ◽  
JunWei Li ◽  
MengWen Jia ◽  
SuHua Zhang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Homology Modeling ◽  
Binding Sites
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