Computer-aided drug design platform using PyMOL

Abstract

The understanding and optimization of protein-ligand interactions are instrumental to medicinal chemists investigating potential drug candidates. Over the past couple of decades, many powerful standalone tools for computer-aided drug discovery have been developed in academia providing insight into protein-ligand interactions. As programs are developed by various research groups, a consistent user-friendly graphical working environment combining computational techniques such as docking, scoring, molecular dynamics simulations, and free energy calculations is needed. Utilizing PyMOL we have developed such a graphical user interface incorporating individual academic packages designed for protein preparation (AMBER package and Reduce), molecular mechanics applications (AMBER package), and docking and scoring (AutoDock Vina and SLIDE). In addition to amassing several computational tools under one interface, the computational platform also provides a user-friendly combination of different programs. For example, utilizing a molecular dynamics (MD) simulation performed with AMBER as input for ensemble docking with AutoDock Vina. The overarching goal of this work was to provide a computational platform that facilitates medicinal chemists, many who are not experts in computational methodologies, to utilize several common computational techniques germane to drug discovery. Furthermore, our software is open source and is aimed to initiate collaborative efforts among computational researchers to combine other open source computational methods under a single, easily understandable graphical user interface.

Bioinformatic and Mutational Analysis of Channelrhodopsin-2 Protein Cation-conducting Pathway

“…Retinal was added in the final models by juxtaposition. The Protein3Dfit server was used for structural superposition (22), and the PyMOL viewer was used for visualization (Schrödinger LLC, Portland, OR) (23). The models underwent energy minimization and a short molecular dynamics simulation (100 ps) with constrained ␣-carbon position to allow the side chain to relax.…”

Targeting the ubiquitin-conjugating enzyme E2D4 for cancer drug discovery–a structure-based approach

“…The solvent accessible surface area (SASA) [58] of the protein before and after docking is calculated with default parameters using Accelrys Discovery Studio Visualizer. The protein-ligand docked structures are analysed and visualized using Accelrys Discovery Studio and PyMoL 1.3 [59]. The The SiteMap module of the Schrödinger suite was used to identify the binding sites of the protein Fig.…”

“…The ADME properties of the ligands were predicted to evaluate the molecules for the druggability (59). All the ligand molecules show ADME properties within the acceptable range as shown in Table 6.…”

New Aryl Derivatives of Acridine with Poly (ADP- Ribose) Polymerase 1 Inhibitory Activity: A Molecular Modeling Approach

“…The three dimensional coordinates of 9 aryl derivatives of acridine were generated and optimized in three dimensional space using the program ACD/ChemSketch (http://www.acdlabs.com/download/chemsk.html) and PyMOL 7.2 [22]. The programs generate the backbone coordinates of the molecules first and then add the side chain atoms.…”