Subject: New linear scaling method

From: "Victor Anisimov" <[email-masked]>
Date: Tue, 15 Apr 2003 09:18:09 +0200

Dear Colleagues,

The cost of drug design is escalating in spite of many strong experimental
techniques emerged last decade, promising the cost saving. Combinatorial
chemistry, gene expression technique have opened new horizons for drug
design but have contributed their part to the continuing growth of the cost,
as well. Thus it seems the task of fulfilling the promise to reduce the cost
of drug design is impossible without the progress being made in the
computational chemistry.

The predictive capability of the computational tools strongly depends on
theoretical methodology employed. The description or real physics of atomic
level phenomena by using the Quantum Mechanics becomes an ultimate
requirement. However a severe limitation of the QM methodology is an
enormous computer resource demand. This requires new ideas being developed
how to avoid the performance bottleneck and the recently created LocalSCF
approach is one of them.

LocalSCF solution of the SCF task is implemented at present for the
semiempirical framework with the thought of quantum chemical calculations of
real life complex proteins. The method represents the first full variational
approach to the linear scaling problem. This makes the method faster, more
stable and more accurate than the traditional cut-off based linear scaling
methods known at present. Developed for a popular PC platform the LocalSCF
can handle 100,000+ atoms real life complex proteins. Thus, for example, 10
steps of full geometry optimization on the 90,000+ protein (Hsluv
Protease-Chaperone Complex, PDB id 1G3I) require 27 hours on a single
processor Pentium-4 / 2.4GHz computer. The method allows simple control for
balancing between speed and accuracy and for validation of the quality of
the density matrix upon selection of a faster calculation mode.

This time I can respond on the old question, which appeared some time ago on
the CCL list, asking what is the biggest system calculated by a QM method?
To the best of my knowledge this is a LocalSCF calculation of the
GroEL-GroES chaperonin complex containing 119,273 atoms (PDB id 1AON). The
energy calculation at the frozen geometry was performed on a regular 32-bit
Windows PC and took 4 hours 30 minutes. The RAM requirement was 1.3GB. If
one had a good molecular structure the 2Gb memory limit would allow
calculating nearly 200,000 atoms real 3D molecular system. Is this enough or
still there is a need to switch to a 64-bit platform?

Besides of the present capabilities the method has strong future
perspectives for those who are interested in developing the method further.
The LocalSCF methodology allows highly effective parallelization of the
code. The ability to treat different parts of the molecule with different
accuracy allows implementation of a full QM alternative to the popular QM/MM
approaches. The LocalSCF method can be extended for the DFT and ab initio
frameworks as well. These are features to be developed.

A brochure describing present capabilities of the computer program is
available on request. The LocalSCF manuscript is submitted for publication
to the Chemical Physics Letters. The preprint of the paper is available from
the Chemistry Preprint Server http://preprint.chemweb.com/physchem/0304005

Please don't hesitate to contact me if there are any questions.

With kind regards,

Victor

--

Victor Anisimov, PhD

FQS Poland, Fujitsu

Krakow, Poland

Tel: +48 12 429-4345, Fax: + 48 12 429-6124

E-mail: [email-masked]