Controlling the shape and flexibility of arylamides: a combined ab initio, ab initio molecular dynamics, and classical molecular dynamics study.
Using quantum chemistry plus ab initio molecular dynamics and classical molecular dynamics methods, we address the relationship between molecular conformation and the biomedical function of arylamide polymers. Specifically, we have developed new torsional parameters for a class of these polymers and applied them in a study of the interaction between a representative arylamide and one of its biomedical targets, the anticoagulant drug heparin. Our main finding is that the torsional barrier of a C(aromatic)-C(carbonyl) bond increases significantly upon addition of an o-OCH2CH2NH3+ substituent on the benzene ring. Our molecular dynamics studies that are based on the original general AMBER force field (GAFF) and GAFF modified to include our newly developed torsional parameters show that the binding mechanism between the arylamide and heparin is very sensitive to the choice of torsional potentials. Ab initio molecular dynamics simulation of the arylamide independently confirms the degree of flexibility we obtain by classical molecular dynamics when newly developed torsional potentials are used.
Pophristic
Vojislava
V
Department of Chemistry and Biochemistry, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania 19104, USA. v.pophri@usip.edu
Vemparala
Satyavani
S
Ivanov
Ivaylo
I
Liu
Zhiwei
Z
Klein
Michael L
ML
DeGrado
William F
WF
D000083:Acetanilides / Q000737:chemistry; D000577:Amides / Q000737:chemistry*; D000925:Anticoagulants / Q000737:chemistry; D001549:Benzamides / Q000737:chemistry; D001555:Benzene Derivatives / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D003198:Computer Simulation; D006493:Heparin / Q000737:chemistry; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D013816:Thermodynamics
D000083:Acetanilides; D000577:Amides; D000925:Anticoagulants; D001549:Benzamides; D001555:Benzene Derivatives; D011108:Polymers; D012996:Solutions; D002244:Carbon; D006493:Heparin; D009584:Nitrogen; C508827:acetanilide; D002118:Calcium