Software and Tools for Computer-Aided Drug Design Research

Computer-Aided Drug Design (CADD) is a practice in modern pharmaceutical investigations. It employs computer-aided techniques in the process of search and development of new drug candidates. By predicting the drug's action with the appropriate target and understanding its molecular interactions, CADD shortens the time and resources needed to seek and create novel therapies or modify the existing therapy. It includes methods such as structure-based and ligand-based drug design, which also helps scientists navigate chemical space, improve leads, and forecast drug activity. CADD instruments are essential at many points of the drug discovery and development process, from target selection to lead optimization, allowing for the efficient and safe design of better drugs.

We can divide this study into two fragments

1. Computational Chemistry (CC)

2. Computer Aided-Drug Design (CADD)

In CC we explore the chemical properties of the structure (drug molecule) such as geometry optimization, spectral behavior, thermodynamic stability, etc. On the other hand in the CADD part we study the chemical compound with protein to find the new drug candidate.

Software and tools used in CADD

Chemical Structure Collection

Small molecule or drug molecule structures can be prepared by ChemDraw software or can be collected from an online server. The server may include ChemSpider, PubChem, etc. And the protein structure is collected from the RCSB protein data bank or other source.

Quantum Mechanics/Molecular Mechanics (QM/MM) Software and Tools

Quantum Mechanics is a fundamental theory that provides the information of the physical properties of nature at scale of atoms and subatomics particles (100-200 atoms).QM works mainly based on two theory ,Wave Function and Density Functional Theory. Wave Function Theory (WFT) methods which are more costly ,the wavefunction of a system and solve the Schrödinger equation for electrons.On the other hand DFT is more advance functions in QM.DFT may include functionals, B3LYP,CAM-B3LYP,M06 , etc.

Molecular Mechanics is applicable for large molecule specially containing thousands of atom.Force filed(Universal Force Field,Amber ,CHARM etc) is applicable for MM.

In this part we study the geometry optimization and spectral characterization by different calculation .

Gaussian

For quantum chemical investigations, computational modeling of molecular systems is essential as it allows researchers to operate at the quantum scale. Determining electrical structures, reaction routes, and other details also requires this.

Other may include, CPMD (Car-Parrinello Molecular Dynamics), ORCA, AMBER, ONIOM (part of Gaussian), TURBOMOLE, NWChem, etc.

3.      Protein Analysis Software

The protein which is collected from the online server is a raw structure,it contains water molecules or hetatom. So for further study (like docking) the protein is cleared or prepared by protein analysis software.

Discovery Studio Visualizer is a protein analysis software developed by BIOVIA used for viewing, analyzing, and improving protein structures, different molecules or macromolecules.It also used in molecular modeling ,finding protein ligand interaction.

4.     Molecular Docking Software

Molecular docking is an important part in drug discovery which allows for predicting the most preferred conformation of the drug ligand bound to the targeted protein or enzyme.Some software and tools are given below.

AutoDock & AutoDock Vina:

One of the commonly utilized approaches in molecular docking which aims at predicting how small molecules, such as drug candidates, bind to a known 3D structure of a receptor. Talk about its ease of use, community support, and performance. Autodock Vina is an improved version of Autodock that focuses on speed and accuracy.

Other tools: SwissDock, GOLD (Genetic Optimization for Ligand Docking), Schrödinger’s Glide, DOCK, Molecular Operating Environment (MOE), FlexX, PLANTS, LeDock, etc. This task can be performed by using a Command prompt in computer if Python is preinstalled.

5.     Molecular dynamics (MD) simulations Software

Molecular dynamics (MD) simulations an another important part of drug discovery that helps to study the physical movements of atoms and drug molecules over time in a simulated environment which mimics the real-life body's physiological conditions and gives insight into the stability, flexibility, and interaction of biomolecules like proteins and ligands.

GROMACS

An MD simulation software that is both very fast and highly scalable. GROMACS is utilized for the study of protein, lipid, and nucleic acid systems.

iMOD

iMOD currently offers a web-based tool for conducting large-scale molecular dynamics simulations, primarily for the analysis of conformational changes in proteins and other biological macromolecules. This server is easy to use. It is primarily used to perform Normal Mode Analysis.

Other software and tools include AMBER, Desmond, CHARMM, LAMMPS, NAMD, TINKER, OpenMM, YASARA, HOOMD-blue, etc.

6.      Visualization Software

To explore the 3D structures of proteins, ligands, and other biomacromolecules these software are used. They help in the analysis or explore molecular interactions, protein-ligand binding, and simulation results. Different Tools or software may be included to perform this section like PyMOL, UCSF Chimera, VMD, MOE, etc.

7.       ADMET Prediction Tools:

ADMET stands for Absorption, Distribution, Metabolism, Excretion, and Toxicity, those parameters are important in drug discovery. They help in evaluating the drug properties whether it is suited for the object or not, and help find drug-likeness, safety, efficacy, etc. There are two most used admet predictor tools, they are admetSAR and pkCSM.Others may include SwissADME, ADMETlab, MetaSite, etc.

8.       Some Other tools and Applications

For drawing different graph we can use MS Excel ,OriginPro software. For drawing different figure,format we can use MS PowerPoint ,Adobe Illustrator and other applications, online tools etc.

This article is taken from the Galen Gazette, October 2024, Issue No. 06. The author, Md Tarikul Islam, is an eight-semester pharmacy student at Comilla University.