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Molecular Modeling and Drug Design Techniques in Microbial Drug Discovery

  • Chandrabose Selvaraj
Chapter

Abstract

Bacterial infection and its resistance have become a major human health concern worldwide, and the number of resistant bacteria is increasing daily. Hence, antibacterial agents should possess the capability of treating resistant infections and have novel mode of action. Conventional drug development approaches are time-consuming and involve huge investments, and they frequently result in failure at the clinical trial phase due side effects. Modern computational approaches are an alternative to conventional modes and are the most effective, greatly improving on the former drug target identification and optimization of the lead compound. In this chapter, we focus on the advent of a few such computational approaches and the classical methods they aid in the identification of potential lead molecules. These techniques may be used as a resource to complement drug discovery programs for novel antibiotic discovery.

Keywords

Microbial resistance Drug Target Multi Drug Resistance Molecular Dynamics Molecular Modeling Ligand Based Screening High Throughput Screening 

Abbreviations

AMR

Antimicrobial resistance

BLAST

Basic Local Alignment Search Tool

CADD

Computer aided drug designing

CG

Coarse-grained

CG-MD

Coarse-grained molecular dynamics

CHARMM

Chemistry at Harvard Macromolecular Mechanics

CoMFA

Comparative molecular field analysis

CoMSIA

Comparative molecular similarity indices analysis

DADA

D-alanyl-D-alanine

DFT

Density functional theory

DPD

Dissipative particle dynamics

ESBLs

Extended spectrum β-lactamases

FDA

Food and Drug Administration

FEP

Free-energy perturbation method

GA

Genetic algorithms

GISA

Glycopeptides-intermediately-resistant S. aureus

GPU

Graphical processor unit

HTS

High throughput screening

IUPAC

International Union of Pure and Applied Chemistry

LB

Ligand-based

LBDD

Ligand-based drug design

LBVS

Ligand-based virtual screening

MD

Molecular dynamics

MDR

Multi-drug resistance

MRSA

Staphylococcus aureus resistant to methicillin

NCBI

National Center for Biotechnology Information

NMR

Nuclear magnetic resonance

PCA

Principle component analysis

PCR

Polymerase chain reaction

PK

Pharmacokinetic

PLS

Partial least squares

QM/MM

Quantum mechanics/molecular mechanics

QSAR

Quantitative structure-activity relationship

SB

Structure-based

SBDD

Structure-based drug design

SBVS

Structure-based virtual screening

SI

Sequence identity

TEIC

Teicoplanin

VANC

Vancomycin

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Chandrabose Selvaraj
    • 1
  1. 1.School of Basic Sciences, Indian Institute of Technology, MandiKamandIndia

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