Computational Drug Discovery and Design

Chapter 13

Molecular Dynamics Simulations of Protein–Drug

Complexes: A Computational Protocol for Investigating

the Interactions of Small-Molecule Therapeutics

with Biological Targets and Biosensors

Jodi A. Hadden and Juan R. Perilla

Abstract

MD simulations provide a powerful tool for the investigation of protein–drug complexes. The following
chapter uses the aryl acylamidase–acetaminophen system as an example to describe a general protocol for
preparing and running simulations of protein–drug complexes, complete with a step-by-step tutorial. The
described approach is broadly applicable toward the study of drug interactions in the context of both
biological targets and biosensing enzymes.

Key wordsDrug development, Drug target, Enzyme biosensors, Force field parameterization,

Molecular dynamics simulation, Protein–drug complex

1 Introduction

Molecular dynamics (MD) simulations use principles of classical

mechanics to predict the motion of particle-based systems. When

applied to the study of biomolecules, particles represent atoms or

groups of atoms. Because of their unique ability to provide a high-

resolution view of biomolecular behavior, MD simulations are

often referred to as the computational microscope [1]. Owing to

recent advances in simulation methodology and supercomputing

technology, the computational microscope is positioned to play a

key role in furthering the field of biomedicine [2].

Small-molecule drugs are a critical aspect of the modern medi-

cal approach to managing public health. Drugs are commonly

employed as therapeutic interventions to treat pathogenic infec-

tion, regulate biological processes that contribute to disease, and

provide pain relief, thereby greatly enhancing quality of life. The

development of new drug compounds represents a major area of

scientific research.

Mohini Gore and Umesh B. Jagtap (eds.),Computational Drug Discovery and Design, Methods in Molecular Biology, vol. 1762,
https://doi.org/10.1007/978-1-4939-7756-7_13,©Springer Science+Business Media, LLC, part of Springer Nature 2018

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