Rational Prediction with Molecular Dynamics for Hit Identification
Sara E. Nichols, Robert V. Swift and Rommie E. Amaro
Affiliation: University of California, San Diego, Howard Hughes Medical Institute, 9500 Gilman Drive, Urey Hall 4202, M/C 0365, La Jolla, CA 92093-0365, USA
Keywords: Computational methods, docking, drug design, flexibility, molecular dynamics, structure-based prediction, validation,
statistical performance analysis.
Although the motions of proteins are fundamental for their function, for pragmatic reasons, the consideration of
protein elasticity has traditionally been neglected in drug discovery and design. This review details protein motion, its
relevance to biomolecular interactions and how it can be sampled using molecular dynamics simulations. Within this context,
two major areas of research in structure-based prediction that can benefit from considering protein flexibility, binding
site detection and molecular docking, are discussed. Basic classification metrics and statistical analysis techniques,
which can facilitate performance analysis, are also reviewed. With hardware and software advances, molecular dynamics
in combination with traditional structure-based prediction methods can potentially reduce the time and costs involved in
the hit identification pipeline.
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