Pasqualoto K. F. M., Ferreira M. M. C., de Santos-Filho O. A., Hopfinger A. J., "CONSTRUCTING PROTEIN PRUNING MODELS TO PERFORM RECEPTOR-DEPENDENT (RD) 4D-QSAR ANALYSIS OF A SET OF DIAZABORINE DERIVATIVES". Ribeirão Preto, SP, Brazil, 25-28/09/2005: 5th International Congress of Pharmaceutical Sciences (CIFARP2005), Braz. J. Pharm. Sci., 41(Suppl 1) (2005), 267. Poster MM006. Section: Molecular Modeling (MM). Poster that was awarded at the CIFARP-2005.
MM006-CONSTRUCTING
PROTEIN PRUNING MODELS TO PERFORM
RECEPTOR-DEPENDENT (RD) 4D-
QSAR ANALYSIS OF A SET
OF DIAZABORINE DERIVATIVES.
KERLY FERNANDA MESQUITA PASQUALOTO1
(PQ); MÁRCIA MIGUEL CASTRO FERREIRA1
(PQ) ; OSVALDO
DE ANDRADE SANTOS-FILHO2
(PQ) ; ANTON J. HOPFINGER2 (PQ)
1UNICAMP
2UIC
Introduction: Receptor pruning is an approach
for achieving reasonable conformational ensemble profile and performing
practical
RD 4D-QSAR analysis in terms of time and computational
resources. Purpose: Reduce the size of a model structure of
enoyl-acp
reductase (ENR) from E. coli,
FabI, to allow ligand-receptor molecular dynamic simulations
(MDSs) to be computationally
economical yet still provide
meaningful binding thermodynamic data. Methodology: Three reduced-size
models of FabI were
created by pruning away all residues greater than 12,
10 and 8 Å radius. The largest
ligand was docked in the active site to define
the largest required receptor model. Energy minimization
and MDSs were carried out using the MOLSIM 3.2 program. The lowest energy
structure for each of receptor models from the MDSs
was compared by root mean square (RMS) fit
to the equivalent
portion of the crystal structure of FabI. Results:
A scale-down 12 Å receptor model of the enzyme
FabI maintains the structural
integrity of the composite parent crystal structure.
Perspectives: Structure-based design of new antituberculosis
agents regarding
the similarity in the active site of two oxidoreductases,
FabI and InhA (M. tuberculosis).
Financial Support: CNPq
Supervisor: Márcia Miguel Castro Ferreira.