UC Berkeley :: EECS :: rluo@uclink

Determine protein structure from amino acid

sequence.Ray Luo

UC Berkeley EECS

UC Berkeley :: EECS :: rluo@uclink

Information flows from DNA to RNA to polypeptide string to folded protein.

Polypeptide:amino acidsequence

Folded protein:3D structure

UC Berkeley :: EECS :: rluo@uclink

Amino acid sequence encodes the 3D structure and function of a protein.

UC Berkeley :: EECS :: rluo@uclink

Comparative methods align sequence against known proteins in a database.

Newprotein

Protein in database

: Protein in database: New proteinAlignment {

UC Berkeley :: EECS :: rluo@uclink

De novo methods search for a stable structure by simulating protein folding.

Folded proteinUnfolded protein

Transition state

- Fr

ee e

nerg

y

Reaction coordinate

UC Berkeley :: EECS :: rluo@uclink

Most proteins have complicated 3D structures requiring efficient algorithms.

De novo

Comparative

UC Berkeley :: EECS :: rluo@uclink

Utilize de novo simulation to support comparative alignment and vice versa.

Proteinfolding

Sequencealignment

SamplingClustering

Cooperative Approach:

UC Berkeley :: EECS :: rluo@uclink

Determine protein structure from amino acid sequence using comparative alignment and protein folding simulation.

Proteinfolding

Sequencealignment