Computational methods for the study of enzymic reaction mechanisms. II. An overlapping mechanically embedded method for hybrid semi-empirical-QM/MM calculations

2003 ◽  
Vol 632 (1-3) ◽  
pp. 247-257 ◽  
Author(s):  
Peter L. Cummins ◽  
Jill E. Gready
Author(s):  
I. A. ADEJORO ◽  
R. O. Ogede ◽  
C. U. Ibeji ◽  
O. O. Adeboye

Theoretical studies on free radical bromination by N-bromosuccinimide were carried out on a range of ethyl-3-methoxy-pyridazine derivatives. The investigations of these reactions performed, in order to develop a convenient and rapid theoretical means of predicting selectivity. The geometry optimizations of the total energies of the reactants and the products were calculated using Semi-empirical; AMI, MNDO, PM3 e Hartree Fock, HF3- 21 G computational methods. The calculation performed using PM3 Hamiltonian gave the best qualitative predictions, thus providing a rapid method for the selectivity of the reactions used in the synthesis of novel heterocyclic analogs of neurotransmitters.


Author(s):  
Hakan Sezgin Sayiner ◽  
Fatma Genç ◽  
Fatma Kandemirli

Drug interactions can have desired, reduced or unwanted effects. The probability of interactions increases with the number of drugs taken. Side effects or therapeutic drug interactions can increase or decrease the effects of one or two drugs. Failure may result from clinically meaningful interactions. Clinicians rarely use foreseeable drug-drug interactions to produce the desired therapeutic effect. For example, when we consider two drugs each causing, peripheral neuropathy increases the likelihood of neuropathy occurrence. In this study geometry optimizations of tigecycline and sulbactam drugs and their combination have been carried out with the evaluation of B3LYP/6-311G (d, p), B3LYP/6-311G (2d, 2p) levels, and the reaction mechanism at semi empirical PM6, which was parameterized for biochemical systems and B3LYP/6-311G (d,p) levels. The main objective of the study is to understand the interaction ofsulbactam with tigecycline, to describe energetic condition of bond formation and electronic structure (orders of the broken and formed bonds). The reaction mechanisms of sulbactam with tigecycline have been studied as stepwise and concerted mechanisms using semi-empircal PM6 and B3LYP/6-311G (d,p) levels.


Biochemistry ◽  
1978 ◽  
Vol 17 (25) ◽  
pp. 5567-5575 ◽  
Author(s):  
Jorge A. Goldstein ◽  
Yak-Fa Cheung ◽  
Michael A. Marletta ◽  
Christopher Walsh

2010 ◽  
Vol 114 (14) ◽  
pp. 5005-5015 ◽  
Author(s):  
Lawrence M. Pratt ◽  
Stewart Voit ◽  
Binh Khanh Mai ◽  
BichLien H. Nguyen

Author(s):  
Timothy Clark ◽  
Peter Gedeck ◽  
Harald Lanig ◽  
Gudrun Schürer

1967 ◽  
Vol 45 (12) ◽  
pp. 2015-2039 ◽  
Author(s):  
R. O. Hurst

A standardized method of treating the analysis of enzymic reaction mechanisms by means of determinant expressions is given. The fully expanded polynomial expressions for systems of order three, four, and five are presented and their use described. Application of the method to the analysis of the effect of dead-end inhibitors on enzymic reactions is discussed and the inhibitor constants are evaluated in terms of the rate constants involved in the inhibition mechanism. Examples are given to demonstrate the contribution that inhibitor studies may make in the search for information concerning the nature of the enzymic reaction mechanism, in the calculation of the rate constants, and in the estimation of the proportion of the enzyme distributed between the different enzyme forms involved in the reaction.


Sign in / Sign up

Export Citation Format

Share Document