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Methods in molecular biology (Clifton, N.J.)
2017;1520 85-106.

Computer-Aided Drug Design Methods.

Wenbo Yu, Alexander D MacKerell
Author Information
  1. Wenbo Yu: Computer-Aided Drug Design Center, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 Penn Street, Baltimore, MD, 21201, USA.
  2. Alexander D MacKerell: Computer-Aided Drug Design Center, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 Penn Street, Baltimore, MD, 21201, USA. alex@outerbanks.umaryland.edu.
PMID: 27873247 DOI: 10.1007/978-1-4939-6634-9_5

Abstract

Computational approaches are useful tools to interpret and guide experiments to expedite the antibiotic drug design process. Structure-based drug design (SBDD) and ligand-based drug design (LBDD) are the two general types of computer-aided drug design (CADD) approaches in existence. SBDD methods analyze macromolecular target 3-dimensional structural information, typically of proteins or RNA, to identify key sites and interactions that are important for their respective biological functions. Such information can then be utilized to design antibiotic drugs that can compete with essential interactions involving the target and thus interrupt the biological pathways essential for survival of the microorganism(s). LBDD methods focus on known antibiotic ligands for a target to establish a relationship between their physiochemical properties and antibiotic activities, referred to as a structure-activity relationship (SAR), information that can be used for optimization of known drugs or guide the design of new drugs with improved activity. In this chapter, standard CADD protocols for both SBDD and LBDD will be presented with a special focus on methodologies and targets routinely studied in our laboratory for antibiotic drug discoveries.

Keywords

Computer-aided drug design Docking Force field Molecular dynamics Pharmacophore SILCS Site identification by ligand competitive saturation Structure-activity relationship Virtual screening

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Grants

  1. R01 CA107331/NCI NIH HHS
  2. R43 GM109635/NIGMS NIH HHS

MeSH Term

Computer-Aided Design
Databases as Topic
Drug Design
Drug Evaluation, Preclinical
Ligands
Molecular Docking Simulation
Quantitative Structure-Activity Relationship
Thermodynamics
User-Computer Interface

Chemicals

Ligands
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 14

Word Cloud

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