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A Constant Time Algorithm for Estimating the Diversity of Large Chemical Libraries

Dimitris K. Agrafiotis
2001 Journal of chemical information and computer sciences  
We describe a novel diversity metric for use in the design of combinatorial chemistry and high-throughput screening experiments.  ...  of a uniform sample using the Kolmogorov-Smirnov statistic.  ...  ACKNOWLEDGMENT The author thanks Dr. Dmitrii N. Rassokhin, Dr. Victor S. Lobanov, and Dr. Sergei Izrailev of 3-Dimensional Pharmaceuticals, Inc., for many useful discussions and Dr. Raymond F.  ... 
doi:10.1021/ci000091j pmid:11206368 fatcat:kw7nbjafbng3pl3csscjqil3xy

EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS

CHARLES K. FISHER, ORLY ULLMAN, COLLIN M. STULTZ
2011 Biocomputing 2012  
We introduce a computationally efficient algorithm called Variational Bayesian Weighting with Structure Selection (VBWSS) for constructing a model for the ensemble of an IDP that contains a minimal number  ...  of conformations and, simultaneously, provides estimates for the uncertainty in properties calculated from the model.  ...  The structural library must be diverse enough to capture the states populated by the IDP, but if it is too large then the problem will be under-restrained, leading to a large posterior uncertainty.  ... 
doi:10.1142/9789814366496_0009 fatcat:hoz2qygipzdcxbzok35zu5ucuy

Efficient construction of disordered protein ensembles in a Bayesian framework with optimal selection of conformations

Charles K Fisher, Orly Ullman, Collin M Stultz
2012 Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing  
We introduce a computationally efficient algorithm called Variational Bayesian Weighting with Structure Selection (VBWSS) for constructing a model for the ensemble of an IDP that contains a minimal number  ...  of conformations and, simultaneously, provides estimates for the uncertainty in properties calculated from the model.  ...  The structural library must be diverse enough to capture the states populated by the IDP, but if it is too large then the problem will be under-restrained, leading to a large posterior uncertainty.  ... 
pmid:22174265 pmcid:PMC3422750 fatcat:p5u6otc2xjajbbumsjnibsyy7m

Multiobjective optimization of combinatorial libraries

D. K. Agrafiotis
2001 IBM Journal of Research and Development  
In this paper, we discuss a class of algorithms for subset selection rooted in the principles of multiobjective optimization.  ...  Designing a combinatorial library is a controversial art that involves a heterogeneous mix of chemistry, mathematics, economics, experience, and intuition.  ...  Soll, and Roger Bone of 3-Dimensional Pharmaceuticals, Inc., for many useful suggestions, and to Dr F. Raymond Salemme for his insightful comments and support of this work.  ... 
doi:10.1147/rd.453.0545 fatcat:vbvq3aouibhxrcg5nzpuyelage

Strategy To Discover Diverse Optimal Molecules in the Small Molecule Universe

Chetan Rupakheti, Aaron Virshup, Weitao Yang, David N. Beratan
2015 Journal of Chemical Information and Modeling  
Soc. 2013, 135, 7296−7303) to develop diversity oriented molecular libraries that can generate a set of compounds that is representative of the small molecule universe and that also biases the library  ...  We show that the approach is efficient compared to exhaustive enumeration and to existing evolutionary algorithms for generating such libraries by testing in the NKp fitness landscape model and in the  ...  We thank OpenEye Scientific Software (Santa Fe, NM) for the use of Omega, OEChem, MolProp, and other tools.  ... 
doi:10.1021/ci500749q pmid:25594586 pmcid:PMC4372820 fatcat:greylj6e2jgyhkyuwjxavhxixa

A computer program for the estimation of protein and nucleic acid sequence diversity in random point mutagenesis libraries

M. J. Volles
2005 Nucleic Acids Research  
a subset of the numerical statistics in libraries of arbitrarily large size.  ...  The program analyzes the generated nucleic acid sequences and/or the associated protein library to produce several estimates of library diversity (number of unique sequences, point mutations, and single  ...  Vr a abioiu and Allegra A. Petti for critical reading of the manuscript and helpful discussions. This work was supported by a Morris K.  ... 
doi:10.1093/nar/gki669 pmid:15990391 pmcid:PMC1166583 fatcat:zu7peezmvjf4ji5dmdkg2kguxa

Chemical ligands, genomics and drug discovery

George R Lenz, Huw M Nash, Satish Jindal
2000 Drug Discovery Today  
Therefore, increasing molecular diversity of a library increases the number of potential target surfaces for scanning and, thus, increases the probability of finding chemical ligands for a target.  ...  Chemical diversity and chemical ligands The reasons for, and the methods of, finding chemical ligands have already been discussed.  ... 
doi:10.1016/s1359-6446(00)01468-9 pmid:10729820 fatcat:adajciynejctnfd2ko6taeosda

Computational design strategies for combinatorial libraries

Sally Rose, Adrian Stevens
2003 Current Opinion in Chemical Biology  
Recent computational advances in statistical methodology, the design of libraries to reduce ADMET problems, targeting protein families and revisiting natural products as sources of inspiration for scaffolds  ...  Medicinal chemistry principles are being increasingly applied to the design of smaller, high purity, information-rich libraries.  ...  Gobbi and Lee [20] have recently refined the algorithm, to reduce the computer time and improve the evenness of the distribution of selected compounds in chemical space.  ... 
doi:10.1016/s1367-5931(03)00057-7 pmid:12826120 fatcat:3d4epsmpi5exzpgqmrqlsh3vei

Design and Prioritization of Plates for High-Throughput Screening

Dimitris K. Agrafiotis, Dmitrii N. Rassokhin
2001 Journal of chemical information and computer sciences  
A general algorithm for the prioritization and selection of plates for high-throughput screening is presented.  ...  The method uses a simulated annealing algorithm to search through the space of plate combinations for the one that maximizes some user-defined objective function.  ...  ACKNOWLEDGMENT The authors thank Drs. Victor S. Lobanov, Sergei Izrailev, and Edward P. Jaeger of 3-Dimensional Pharmaceuticals, Inc., for many useful suggestions, and Dr. Raymond F.  ... 
doi:10.1021/ci000313d pmid:11410060 fatcat:nb2tynni6jbz3pdvcdvdcn6qym

Monte Carlo Methods for Small Molecule High-Throughput Experimentation

Ligang Chen, Michael W. Deem
2001 Journal of chemical information and computer sciences  
By analogy with Monte Carlo algorithms, we propose new strategies for design and redesign of small molecule libraries in high-throughput experimentation, or combinatorial chemistry.  ...  Although the best compounds identified by the genetic algorithm are comparable to those from the better Monte Carlo schemes, the diversity of favorable compounds identified is reduced by roughly 60%.  ...  The diversity of the library will change as the library changes. A larger library will generally possess a higher absolute diversity simply due to the increased number of compounds.  ... 
doi:10.1021/ci000151l pmid:11500111 fatcat:xfthfdxbcnfdbaakwlf2vpb5ty

Computational Challenges of Structure-Based Approaches Applied to HIV [chapter]

Stefano Forli, Arthur J. Olson
2015 Current Topics in Microbiology and Immunology  
Acknowledgments We thank IBM World Community Grid for the computational resource support provided to the FightAIDS@Home project. This work was supported by NIH R01 GM073087 and P50 GM103368 to AJO.  ...  From the perspective of chemical diversity, fragment libraries can be considered diversity libraries, where combinations of a relatively small number of molecules (1-10K compounds) cover a large chemical  ...  Another common approach to build a diversity library is to remove structural redundancy, i.e., removing ligands with similar structure, and maximizing structural and chemical diversity of the set.  ... 
doi:10.1007/82_2015_432 pmid:25711462 fatcat:6yiwypppbbgt5jrojt4a2k44dq

A reproducibility study of "Augmenting Genetic Algorithms with Deep Neural Networks for Exploring the Chemical Space" [article]

Kevin Maik Jablonka, Fergus Mcilwaine, Susana Garcia, Berend Smit, Brian Yoo
2021 arXiv   pre-print
Nigam et al. reported a genetic algorithm (GA) utilizing the SELFIES representation and also propose an adaptive, neural network-based penalty that is supposed to improve the diversity of the generated  ...  The main claims of the paper are that this GA outperforms other generative techniques (as measured by the penalized logP) and that a neural network-based adaptive penalty increases the diversity of the  ...  Since a large pool of diverse molecules is quite relevant for applications with high failure rates (e.g., drug discovery), we propose the addition of penalty terms of the form 1 − internal population diversity  ... 
arXiv:2102.00700v3 fatcat:ng3mxtkg4vfq3keln5awlwiilq

New Paradigms in Drug Design and Discovery

Nouri Neamati, Joseph Barchi,Jr.
2002 Current Topics in Medicinal Chemistry  
In addition, several new therapeutic agents have been developed in the latter part of the 20 th century that have improved our quality of life and increased our overall survival time.  ...  The new millennium has ushered in an era of science that will revolutionize a great majority of our daily activities.  ...  A key requirement for a successful virtual screening is accession to a large and a diverse library or a database.  ... 
doi:10.2174/1568026023394227 pmid:11944817 fatcat:naskbpapmrcgxihg5zhvcbwhui

New Paradigms in Drug Design and Discovery

Joseph J. Barchi Jr., Nouri Neamati
2004 Frontiers in Medicinal Chemistry - Online  
In addition, several new therapeutic agents have been developed in the latter part of the 20 th century that have improved our quality of life and increased our overall survival time.  ...  The new millennium has ushered in an era of science that will revolutionize a great majority of our daily activities.  ...  A key requirement for a successful virtual screening is accession to a large and a diverse library or a database.  ... 
doi:10.2174/1567204043396398 fatcat:2avlru3txrclvmsdy63ujbub2a

Similarity and Dissimilarity Methods for Processing Chemical Structure Databases

V. J. Gillet
1998 Computer journal  
This paper reviews measures of similarity and dissimilarity between pairs of chemical molecules and the use of such measures for processing chemical databases.  ...  The paper then discusses recent work on the calculation of similarity by aligning molecular fields and on the selection of structurally diverse subsets of chemical databases.  ...  The Krebs Institute for Biomolecular Research is a designated Biomolecular Sciences Centre of the Biotechnology and Biological Sciences Research Council.  ... 
doi:10.1093/comjnl/41.8.547 fatcat:clvxe7eks5hwrikgyz7tezxf5e
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