Representing Receptor Flexibility in Ligand Docking through Relevant Normal Modes

2005 ◽  
Vol 127 (26) ◽  
pp. 9632-9640 ◽  
Author(s):  
Claudio N. Cavasotto ◽  
Julio A. Kovacs ◽  
Ruben A. Abagyan
Keyword(s):  
Normal Modes ◽  
Ligand Docking ◽  
Receptor Flexibility

GANM: A protein–ligand docking approach based on genetic algorithm and normal modes

2012 ◽  
Vol 219 (2) ◽  
pp. 511-520 ◽  
Author(s):  
Angélica Nakagawa Lima ◽  
Eric Allison Philot ◽  
David Perahia ◽  
Antonio Sérgio Kimus Braz ◽  
Luis P.B. Scott
Keyword(s):  
Genetic Algorithm ◽  
Normal Modes ◽  
Ligand Docking ◽  
Docking Approach

scholarly journals Four-Dimensional Docking: A Fast and Accurate Account of Discrete Receptor Flexibility in Ligand Docking

2009 ◽  
Vol 52 (2) ◽  
pp. 397-406 ◽  
Author(s):  
Giovanni Bottegoni ◽  
Irina Kufareva ◽  
Maxim Totrov ◽  
Ruben Abagyan
Keyword(s):  
Ligand Docking ◽  
Receptor Flexibility

Evaluation of Grey Wolf Optimization Algorithm on Rigid and Flexible Receptor Docking

2020 ◽  
Author(s):  
Kin Meng Wong ◽  
Shirley Siu
Keyword(s):  
Scoring Function ◽  
Ligand Docking ◽  
Receptor Protein ◽  
Pose Prediction ◽  
Grey Wolf ◽  
Success Rates ◽  
Autodock Vina ◽  
Grey Wolf Optimization ◽  
Structure Based Drug Design ◽  
Docking Program

Protein-ligand docking programs are indispensable tools for predicting the binding pose of a ligand to the receptor protein in current structure-based drug design. In this paper, we evaluate the performance of grey wolf optimization (GWO) in protein-ligand docking. Two versions of the GWO docking program – the original GWO and the modified one with random walk – were implemented based on AutoDock Vina. Our rigid docking experiments show that the GWO programs have enhanced exploration capability leading to significant speedup in the search while maintaining comparable binding pose prediction accuracy to AutoDock Vina. For flexible receptor docking, the GWO methods are competitive in pose ranking but lower in success rates than AutoDockFR. Successful redocking of all the flexible cases to their holo structures reveals that inaccurate scoring function and lack of proper treatment of backbone are the major causes of docking failures.

DPP-IV Inhibitory Phenanthridines: Ligand, Structure-Based Design and Synthesis

2020 ◽  
Vol 16 (3) ◽  
pp. 295-307
Author(s):  
Reema A. Khalaf ◽  
Dalal Masalha ◽  
Dima Sabbah
Keyword(s):  
Pharmacophore Model ◽  
Pharmacophore Modeling ◽  
Ligand Docking ◽  
Health Concern ◽  
Aromatic Rings ◽  
Oral Antidiabetic Agents ◽  
Design And Synthesis ◽  
Dpp Iv ◽  
Novel Scaffold

Background: Lately, diabetes has become the main health concern for millions of people around the world. Dipeptidyl peptidase-IV (DPP-IV) inhibitors have emerged as a new class of oral antidiabetic agents. Formerly, acridines, N4-sulfonamido-succinamic, phthalamic, acrylic and benzoyl acetic acid derivatives, and sulfamoyl-phenyl acid esters were designed and developed as new DPP-IV inhibitors. Objective: This study aims to develop a pharmacophore model of DPP-IV inhibitors and to evaluate phenanthridines as a novel scaffold for inhibiting DPP-IV enzyme. In addition, to assess their binding interactions with the enzyme through docking in the binding site of 4A5S (PDB). Methods: Herein, Quantum–Polarized Ligand Docking (QPLD) and ligand-based pharmacophore modeling investigations were performed. Three novel 3,8-disubstituted-6-phenyl phenanthridine derivatives 3-5 have been designed, synthesized and characterized. In vitro biological testing against DPP-IV was carried out using fluorometric assay kit. Results: QPLD study demonstrates that compounds 3-5 forms H-bond with Lys554, Trp629, and Tyr631, besides charge transfer interaction between their aromatic rings and the aromatic rings of Tyr547 and Tyr666. Moreover, they fit the three pharmacophoric point features of DPP-IV inhibitors and were proven to have in vitro DPP-IV inhibitory activity where compound 5 displayed a % inhibition of 45.4 at 100 μM concentration. Conclusion: Phenanthridines may serve as a potential lead compound for developing new DPP-IV inhibitors as a promising antidiabetic agent. Computational results suggest future structural simplification.

Application of Molecular Docking for the Development of Improved HIV-1 Reverse Transcriptase Inhibitors

2020 ◽  
Vol 16 ◽  
Author(s):  
Arash Soltani ◽  
Seyed Isaac Hashemy ◽  
Farnaz Zahedi Avval ◽  
Houshang Rafatpanah ◽  
Seyed Abdolrahim Rezaee ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Binding Capacity ◽  
Binding Pocket ◽  
Ligand Docking ◽  
Binding Modes ◽  
Wild Type ◽  
Parent Molecule ◽  
Discovery Studio ◽  
Approved Drugs ◽  
Hiv 1

Introoduction: Inhibition of the reverse transcriptase (RT) enzyme of human immunodeficiency virus (HIV) by low molecular weight inhibitors is still an active area of research. Here, protein-ligand interactions and possible binding modes of novel compounds with the HIV-1 RT binding pocket (the wild-type as well as Y181C and K103N mutants) were obtained and discussed. Methods: A molecular fragment-based approach using FDA-approved drugs were followed to design novel chemical derivatives using delavirdine, efavirenz, etravirine and rilpivirine as the scaffolds. The drug-likeliness of the derivatives was evaluated using Swiss-ADME. Then the parent molecule and derivatives were docked into the binding pocket of related crystal structures (PDB ID: 4G1Q, 1IKW, 1KLM and 3MEC). Genetic Optimization for Ligand Docking (GOLD) Suite 5.2.2 software was used for docking and the results analyzed in the Discovery Studio Visualizer 4. A derivative was chosen for further analysis, if it passed drug-likeliness and the docked energy was more favorable than that of its parent molecule. Out of the fifty-seven derivatives, forty-eight failed in druglikeness screening by Swiss-ADME or in docking stage. Results: The final results showed that the selected compounds had higher predicted binding affinities than their parent scaffolds in both wild-type and the mutants. Binding energy improvement was higher for the structures designed based on second-generation NNRTIs (etravirine and rilpivirine) than the first-generation NNRTIs (delavirdine and efavirenz). For example, while the docked energy for rilpivirine was -51 KJ/mol, it was improved for its derivatives RPV01 and RPV15 up to -58.3 and -54.5 KJ/mol, respectively. Conclusion: In this study, we have identified and proposed some novel molecules with improved binding capacity for HIV RT using fragment-based approach.

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