Applications of Discrete Molecular Dynamics in biology and medicine.

Discrete Molecular Dynamics (DMD) is a physics-based simulation method using discrete energetic potentials rather than traditional continuous potentials, allowing microsecond time scale simulations of biomolecular systems to be performed on personal computers rather than supercomputers or specialized hardware. With the ongoing explosion in processing power even in personal computers, applications of DMD have similarly multiplied. In the past two years, researchers have used DMD to model structures of disease-implicated protein folding intermediates, study assembly of protein complexes, predict protein-protein binding conformations, engineer rescue mutations in disease-causative protein mutants, design a protein conformational switch to control cell signaling, and describe the behavior of polymeric dispersants for environmental cleanup of oil spills, among other innovative applications.

[1]  F. Ding,et al.  Discrete Molecular Dynamics Simulation of Biomolecules , 2012 .

[2]  D. Ladner,et al.  Structure-function relationship of PAMAM dendrimers as robust oil dispersants. , 2014, Environmental Science and Technology.

[3]  N. Dokholyan,et al.  ApoE 4-specific misfolded intermediate identified by molecular dynamics simulations , 2015 .

[4]  F. Ding,et al.  Local unfolding of Cu, Zn superoxide dismutase monomer determines the morphology of fibrillar aggregates. , 2012, Journal of molecular biology.

[5]  Kevin M. D'Auria,et al.  Structural and dynamic determinants of protein-peptide recognition. , 2011, Structure.

[6]  H. Stanley,et al.  Discrete molecular dynamics studies of the folding of a protein-like model. , 1998, Folding & design.

[7]  S. Shabalina,et al.  Disruptive mRNA folding increases translational efficiency of catechol-O-methyltransferase variant , 2011, Nucleic acids research.

[8]  C. Anfinsen.  Principles that govern the folding of protein chains. , 1973, Science.

[9]  Pradeep Kota,et al.  Rational coupled dynamics network manipulation rescues disease-relevant mutant cystic fibrosis transmembrane conductance regulator , 2014, Chemical science.

[10]  Modesto Orozco,et al.  Exploration of conformational transition pathways from coarse-grained simulations , 2013, Bioinform..

[11]  E. Salonen,et al.  Effect of fullerenol surface chemistry on nanoparticle binding-induced protein misfolding. , 2014, Nanoscale.

[12]  B. Urbanc,et al.  Discrete molecular dynamics study of oligomer formation by N-terminally truncated amyloid β-protein. , 2013, Journal of molecular biology.

[13]  Alexander Tropsha,et al.  Discrete Molecular Dynamics Distinguishes Nativelike Binding Poses from Decoys in Difficult Targets , 2022 .

[14]  F. Ding,et al.  Ab initio RNA folding by discrete molecular dynamics: from structure prediction to folding mechanisms. , 2008, RNA.

[15]  N. Dokholyan.  Computational modeling of biological systems : from molecules to pathways , 2012 .

[16]  F. Ding,et al.  New models of Tetrahymena telomerase RNA from experimentally derived constraints and modeling. , 2012, Journal of the American Chemical Society.

[17]  N. Dokholyan,et al.  Traffic within the cytochrome b6f lipoprotein complex: gating of the quinone portal. , 2014, Biophysical journal.

[18]  Albert Solernou,et al.  Efficient Relaxation of Protein-Protein Interfaces by Discrete Molecular Dynamics Simulations. , 2013, Journal of chemical theory and computation.

[19]  B. Alder,et al.  Studies in Molecular Dynamics. I. General Method , 1959 .

[20]  Pradeep Kota,et al.  Engineered Allosteric Activation of Kinases in Living Cells , 2011 .

[21]  N. Dokholyan,et al.  Energetic and structural basis for activation of the epithelial sodium channel by matriptase. , 2012, Biochemistry.

[22]  Feng Ding,et al.  Discrete molecular dynamics: an efficient and versatile simulation method for fine protein characterization. , 2012, The journal of physical chemistry. B.

[23]  Christopher A. Lavender,et al.  Three-Dimensional RNA Structure Refinement by Hydroxyl Radical Probing , 2012, Nature Methods.

[24]  Nikolay V. Dokholyan,et al.  ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations , 2015, PLoS Comput. Biol..

[25]  F. Ding,et al.  Discrete molecular dynamics , 2012 .

[26]  Feng Ding,et al.  Rational design of a ligand-controlled protein conformational switch , 2013, Proceedings of the National Academy of Sciences.

[27]  Discrete molecular dynamics study of oligomer formation by N-terminally truncated amyloid β-protein. , 2013, Journal of molecular biology.

[28]  R. Broglia,et al.  The maturation of HIV‐1 protease precursor studied by discrete molecular dynamics , 2014, Proteins.

[29]  Justin L. Black,et al.  Identification of novel integrin binding partners for calcium and integrin binding protein 1 (CIB1): structural and thermodynamic basis of CIB1 promiscuity. , 2013, Biochemistry.

[30]  Feng Ding,et al.  Native-like RNA tertiary structures using a sequence-encoded cleavage agent and refinement by discrete molecular dynamics. , 2009, Journal of the American Chemical Society.

[31]  Nikolay V. Dokholyan,et al.  Discrete Molecular Dynamics Can Predict Helical Prestructured Motifs in Disordered Proteins , 2014, PloS one.

[32]  Feng Ding,et al.  Fidelity of the protein structure reconstruction from inter-residue proximity constraints. , 2007, The journal of physical chemistry. B.

[33]  M. Karplus,et al.  Folding thermodynamics of a model three-helix-bundle protein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Martin C. Herbordt,et al.  Parallel discrete molecular dynamics simulation with speculation and in-order commitment , 2011, J. Comput. Phys..

[35]  The Phylogenetic Distribution and Evolution of Enzymes Within the Thymidine Kinase 2-like Gene Family in Metazoa , 2014, Journal of Molecular Evolution.