The errors of our ways: taking account of error in computer-aided drug design to build confidence intervals for our next 25 years
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The future of the advancement as well as the reputation of computer-aided drug design will be guided by a more thorough understanding of the domain of applicability of our methods and the errors and confidence intervals of their results. The implications of error in current force fields applied to drug design are given are given as an example. Even as our science advances and our hardware become increasingly more capable, our software will be perhaps the most important aspect in this realization. Some recommendations for the future are provided. Education of users is essential for proper use and interpretation of computational results in the future.
KeywordsError Precision Force fields Computational chemistry Drug discovery Drug design Computer-aided drug design Molecular modeling Molecular dynamics Crystal structure prediction
Many thanks to Marvin Waldman, Anthony Nicholls, Robert Clark, and Yvonne Martin for an insightful review of and contributions to the manuscript. Thanks to David Mobley and John Chodera for sharing their results. The author is indebted to Donald Williams, Marvin Waldman, Sarah Price, Carl Ewig, Arnold Hagler, Shneior Lifson, Peter Kollman, Jay Ponder, Alexander MacKerell, Bernard Brooks, and many others for teaching him about the underbelly of force fields. My appreciation to Anthony Nicholls, Marvin Waldman, William Swope, Julia Rice, Richard Friesner and Thomas Halgren for always invigorating discussions.
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