Subject: Re: Inverse folding...

From: [email-masked] (Rick Lee )
Date: Wed, 21 Sep 94 09:59:31 -0700

>From: David Clark <[email-masked]>
>Date: Tue, 13 Sep 94 14:16:44 -0100
>To: [email-masked]
>Subject: CCL:Inverse folding/sequence threading/de novo folding software
>Sender: [email-masked]
>Errors-To: [email-masked]
>Precedence: bulk
>
>
>Dear All
>
>Is anyone aware of any available software (commercial or otherwise)
>for inverse protein folding/sequence threading or de novo folding?
>I'm aware of TRIPOS' Matchmaker program but would be interested to
>know of any others.
>
>Many thanks
>
>David E. Clark

Biosym offers Profiles-3D, a program to assess the compatibility between
amino acid sequences and three-dimensional structures. The program employs
the method of David Eisenberg of UCLA, which analyzes structures in terms
of the residues' local environments. Environments are classified in terms
of secondary structure, solvent accessibility, and polar/apolar neighbors.
Thus any 3D structure can be reduced to a 1D string of environment classes.
After examining a set of well characterized globular proteins, a table of
propensities for each of the 20 amino acids to be in each of the environment
classes was developed. This 3D-1D scoring table can be used to measure a
compatibility score and perform an alignment between a given sequence and
structure.

The scoring method can be used in 3 ways: 1) A single amino acid sequence
can be compared to a database of pre-calculated 3D profiles (the environments
for the structures combined with the scoring table). The database is comprised
of all known structures from the Brookhaven PDB. This techniques is valuable
for finding reference (template) structures from which to build homology
models. 2) A given structure can be compared to a sequence database to study
evolutionary relationships. 3) A built structure can be compared with
its own sequence to assess the quality of the model. Since there are no
insertions or deletions, the score needs no normalizing, and so it can be
calculated on a residue by residue basis. Thus local areas of misfolding, or
hotspots, can be identified.

================================================================
   Richard H. Lee, Ph.D.              (e-mail: [email-masked])
   Lead Scientist, Protein Modeling

   Biosym Technologies, Inc.              Phone: (619) 546-5536
   9685 Scranton Road                     Fax:   (619) 458-0136
   San Diego, CA  92121-2777 USA
================================================================