David Watson

Questions and Answers (5) View all

• Answer added in Homology Modeling
  57 Can you recommend any homology modeling tools?
  By Priyanka Kshirsagar · Solapur University
  David Watson · University of Mississippi

  You may also want to try out I-tasser for automated homology model development, depending upon your target. 

  You may also want to try out I-tasser for automated homology model development, depending upon your target.
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• Answer added in Modeling and Docking
  3 What is molecular dynamics and simulation?
  By Prasanna Ranade · University of Mumbai
  David Watson · University of Mississippi

  Molecular dynamics is an atomistic method of simulating the movement of molecules over (usually relatively short) time scales. It is predominantly use... [more]

  Molecular dynamics is an atomistic method of simulating the movement of molecules over (usually relatively short) time scales. It is predominantly used in the simulation of protein movements either with or without accompanying small molecules (ligands), cofactors, and allosteric modulators. One of the major goals of MD is to determine the stability or energetics of macromolecules as they interact with solvent and/or ligands. Over a sufficiently long enough time scale, a well designed simulation may provide insights into how molecules move, including information that can be extrapolated from the microscopic to the macroscopic level. Properties such as density, entropy, energy, and so on may be calculated by taking "snapshots" of the trajectory of the atoms in such a simulation.
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• Answer added in Modeling and Docking
  2 How to interpret Docking results?
  By Talal Awad · sudan academy of science
  David Watson · University of Mississippi

  My first question is whether or not you performed a validation with the native ligand, if applicable. Did it dock sufficiently close to the native cry... [more]

  My first question is whether or not you performed a validation with the native ligand, if applicable. Did it dock sufficiently close to the native crystal structure? Of course, if you are using a homology model, then there are whole host of other issues you need to worry about. Are there important waters in the vicinity of the ligand in the crystal structure? What about waters in homologous proteins or isoforms of your target? Rank ordering is but one of many ways of rationalizing the validity of a model. You might want to look at the similarity of the scaffolds that you are docking, and propose overall binding modes based upon that kind of analysis. You may also want to question whether or not there are highly-flexible side chains, which can be assessed from the B-factors in the original PDB file. Normal mode analysis may give you some insight into the characteristic motions of the protein in the vicinity of the orthosteric site. As for docking scores, they depend to an extent on the implementation of the software, and some targets are better treated with one type of scoring or software than others. Hydrogen bonding and electrostatics are a major driving force and may tend to overoptimistically place one compound in an unexpected binding mode ahead of others in the native state that have an abundance of "shape complementarity". These may be valid alternative binding modes and the interpretation is going to be up to you.
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• Answer added in Medicinal and Pharmaceutical Chemistry
  9 Can anyone suggest drugs regarding Triazoles and Oxadiazole available commercially?
  By Mohana Rao Katiki · Indian Institute of Chemical Technology
  David Watson · University of Mississippi

  One approach may be to search at drugbank.ca using a SMILES string. There may even be a way to limit the search to approved drugs. 

  One approach may be to search at drugbank.ca using a SMILES string. There may even be a way to limit the search to approved drugs.

  http://www.drugbank.ca/ ×

  DrugBank
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• Answer added in QSAR
  4 reliable method for outlier detection and elimination in 3D QSAR CoMFA?
  By Nirzari Gupta · Nirma University
  David Watson · University of Mississippi

  If you intend to reject outliers, there should be justifiable reason to do so, and rejections should be documented. Some outliers can provide valuable... [more]

  If you intend to reject outliers, there should be justifiable reason to do so, and rejections should be documented. Some outliers can provide valuable insights into alternative binding modes, activity cliffs, "magic methyl" groups, and so on. It would be unfortunate to overlook these data in order to build a model with desirable validation parameters.
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