The accelerated pace of genomic sequencing has
increased the demand for structural models of gene products.
Improved quantitative methods are needed to study the many
systems (e.g., macromolecular assemblies) for which data
are scarce. Here, we describe a new molecular dynamics
method for protein structure determination and molecular
modeling. An energy function, or database potential, is
derived from distributions of interatomic distances obtained
from a database of known structures. X-ray crystal structures
are refined by molecular dynamics with the new energy function
replacing the Van der Waals potential. Compared to standard
methods, this method improved the atomic positions, interatomic
distances, and side-chain dihedral angles of structures
randomized to mimic the early stages of refinement. The
greatest enhancement in side-chain placement was observed
for groups that are characteristically buried. More accurate
calculated model phases will follow from improved interatomic
distances. Details usually seen only in high-resolution
refinements were improved, as is shown by an R-factor
analysis. The improvements were greatest when refinements
were carried out using X-ray data truncated at 3.5 Å.
The database potential should therefore be a valuable tool
for determining X-ray structures, especially when only
low-resolution data are available.