Abstract: This paper presents a computer aided design method useful for
simulation of a set of proteolytic cleavages upon target proteins obtained from
the Brookhaven Data Bank. The method was developed by using algorithms that are
able to interface themselves with other software environments, in order to
assist computer analyses in the molecular modelling field, and allowing the
generation of molecular libraries containing protein fragments produced by
simulated proteolysis. These libraries include structures that differ for
several amino acid deletions upon specified regions of the primary sequence.
Target residues chosen for the simulation are compatible with enzymatic
proteolysis methods used in conventional laboratory procedures. Furthermore,
algorithms were able to identify a set of chemical-physical properties of the
starting proteins, leading the simulation to find out the most suitable
residues for proteolysis. The goal of these strategies is to generate fragments
that are leaded to maintain the native-like condition of starting molecules,
avoiding loss of conformational characteristics of the original tertiary
structure. Proteins chosen for generating proteolytic libraries were
represented by naphthalene 1,2 dioxygenase and Rigidoporus lignosus
laccase.
Keywords: Molecular library generation, molecular modelling, closed loops, virtual proteolysis, screening and fragmentation, leading proteins, target amino acids, hydrophobic profile, secondary structure, sequence comparison, folding pathway, PDB files, NDO, RI laccase, 3D structures detection, enzymatic cleavage, protein design, laboratory procedures, soil bioremedation
