2 research outputs found
Interactive drug-design: using advanced computing to evaluate the induced fit effect
This thesis describes the efforts made to provide protein flexibility in a molecular modelling
software application, which prior to this work, was operating using rigid proteins and semi
flexible ligands. Protein flexibility during molecular modelling simulations is a non-‐trivial
task requiring a great number of floating point operations and it could not be accomplished
without the help of supercomputing such as GPGPUs (or possibly Xeon Phi).
The thesis is structured as follows. It provides a background section, where the reader can
find the necessary context and references in order to be able to understand this report.
Next is a state of the art section, which describes what had been done in the fields of
molecular dynamics and flexible haptic protein ligand docking prior to this work. An
implementation section follows, which lists failed efforts that provided the necessary
feedback in order to design efficient algorithms to accomplish this task.
Chapter 6 describes in detail an irregular – grid decomposition approach in order to provide
fast non-‐bonded interaction computations for GPGPUs. This technique is also associated
with algorithms that provide fast bonded interaction computations and exclusions handling
for 1-‐4 bonded atoms during the non-‐bonded forces computation part. Performance
benchmarks as well as accuracy tables for energy and force computations are provided to
demonstrate the efficiency of the methodologies explained in this chapter.
Chapter 7 provides an overview of an evolutionary strategy used to overcome the problems
associated with the limited capabilities of local search strategies such as steepest descents,
which get trapped in the first local minima they find. Our proposed method is able to
explore the potential energy landscape in such a way that it can pick competitive uphill
solutions to escape local minima in the hope of finding deeper valleys. This methodology
is also serving the purpose of providing a good number of conformational updates such
that it is able to restore the areas of interaction between the protein and the ligand while
searching for optimum global solutions