2 research outputs found
Automated Large-Scale File Preparation, Docking, and Scoring: Evaluation of ITScore and STScore Using the 2012 Community Structure–Activity Resource Benchmark
In
this study, we use the recently released 2012 Community Structure–Activity
Resource (CSAR) data set to evaluate two knowledge-based scoring functions,
ITScore and STScore, and a simple force-field-based potential (VDWScore).
The CSAR data set contains 757 compounds, most with known affinities,
and 57 crystal structures. With the help of the script files for docking
preparation, we use the full CSAR data set to evaluate the performances
of the scoring functions on binding affinity prediction and active/inactive
compound discrimination. The CSAR subset that includes crystal structures
is used as well, to evaluate the performances of the scoring functions
on binding mode and affinity predictions. Within this structure subset,
we investigate the importance of accurate ligand and protein conformational
sampling and find that the binding affinity predictions are less sensitive
to non-native ligand and protein conformations than the binding mode
predictions. We also find the full CSAR data set to be more challenging
in making binding mode predictions than the subset with structures.
The script files used for preparing the CSAR data set for docking,
including scripts for canonicalization of the ligand atoms, are offered
freely to the academic community
Computation and Simulation of the Structural Characteristics of the Kidney Urea Transporter and Behaviors of Urea Transport
Urea transporters
are a family of membrane proteins that transport
urea molecules across cell membranes and play important roles in a
variety of physiological processes. Although the crystal structure
of bacterial urea channel <i>dv</i>UT has been solved, there
lacks an understanding of the dynamics of urea transport in <i>dv</i>UT. In this study, by using molecular dynamics simulations,
Monte Carlo methods, and the adaptive biasing force approach, we built
the equilibrium structure of <i>dv</i>UT, calculated the
variation in the free energy of urea, determined the urea-binding
sites of <i>dv</i>UT, gained insight into the microscopic
process of urea transport, and studied the water permeability in <i>dv</i>UT including the analysis of a water chain in the pore.
The strategy used in this work can be applied to studying transport
behaviors of other membrane proteins