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Structural properties and interaction energies affecting drug design. An approach combining molecular simulations, statistics, interaction energies and neural networks

Paper ID Volume ID Publish Year Pages File Format Full-Text
15051 1370 2015 6 PDF Available
Title
Structural properties and interaction energies affecting drug design. An approach combining molecular simulations, statistics, interaction energies and neural networks
Abstract

•Molecular dynamics simulations were run on PDB structures containing protein and ligand.•Interaction and structural parameters were extracted from the structures.•Linear regression was used to check for correlation between these parameters.•A neural network (NN) was used to predict ligand design parameters based on the protein.•The NN performance improved when tweaking the protein structural parameters used.

In order to elucidate some basic principles for protein–ligand interactions, a subset of 87 structures of human proteins with their ligands was obtained from the PDB databank. After a short molecular dynamics simulation (to ensure structure stability), a variety of interaction energies and structural parameters were extracted. Linear regression was performed to determine which of these parameters have a potentially significant contribution to the protein–ligand interaction. The parameters exhibiting relatively high correlation coefficients were selected. Important factors seem to be the number of ligand atoms, the ratio of N, O and S atoms to total ligand atoms, the hydrophobic/polar aminoacid ratio and the ratio of cavity size to the sum of ligand plus water atoms in the cavity. An important factor also seems to be the immobile water molecules in the cavity. Nine of these parameters were used as known inputs to train a neural network in the prediction of seven other. Eight structures were left out of the training to test the quality of the predictions. After optimization of the neural network, the predictions were fairly accurate given the relatively small number of structures, especially in the prediction of the number of nitrogen and sulfur atoms of the ligand.

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Keywords
PDB, Protein Data Bank; MDS, molecular dynamics simulation; EM, energy minimization; MDS + EM, molecular dynamics simulation followed by energy minimizationDrug design; Molecular dynamics simulation; Interaction energy; Neural networks
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Structural properties and interaction energies affecting drug design. An approach combining molecular simulations, statistics, interaction energies and neural networks
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 56, June 2015, Pages 7–12
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us