Homology Protein Structure Modeling. Andrej Sali, Roberto Sanchez, Azat Badretdinov. Rockefeller University, 1230 York Avenue, New York, NY 10021, USA; e-mail sali@rockvax.rockefeller.edu

Our approach to comparative protein structure modeling based on satisfaction of spatial restraints will be described and evaluated. Recent improvements of sequence-structure alignments, the modeling of loops and sidechains, and of model evaluation will be discussed. In the first stage of the method, the alignment between the sequence to be modeled and related template structures is obtained. In the second stage, restraints on various distances, angles, and dihedral angles in the sequence are derived from its alignment with the template structures and from more general considerations. The restraints are expressed in the form of conditional probability density functions. And finally, the 3D model is obtained by minimizing violations of homology-derived and energy restraints, using conjugate gradients and molecular dynamics procedures. The method has been implemented in the MODELLER program that is available on Internet at URL http://guitar.rockefeller.edu/.