System for molecular packing calculations

Patent metadata

Field	Value
Publication number	US-10832794-B2
Application number	US-201113822258-A
Country	US
Kind code	B2
Filing date	Sep 22, 2011
Priority date	Sep 24, 2010
Publication date	Nov 10, 2020
Grant date	Nov 10, 2020

Abstract

The invention provides a computer implemented method of quantifying the quality of packing for a residue comprising one or more residue atoms in a first protein in a first conformation, the method comprising: (a) calculating one or more close contact potentials based on a distance between the one or more residue atoms and one or more environment atoms, (b) calculating a contact area of the one or more residue atoms that is exposed to the one or more environment atoms and (c) calculating a close contact surface density (CCSD) by dividing the sum of the one or more close contact potentials by the contact area.

First claim

I claim:

1. A method of engineering a variant protein relative to a parent protein, the parent protein comprising a first residue comprising one or more residue atoms, the method comprising:
(a) calculating a summation of one or more close contact potentials of the parent protein based on respective distances between the one or more residue atoms of the first residue of the parent protein and one or more environment atoms of the one or more residue atoms of the first residue of the parent protein, in accordance with a close contact potential formula of the form:

U

a
⁢
b

⁡

(

r

a
⁢
b

)

⁢

=

{

1

if
⁢

⁢

r

a
⁢
b

<

r
c

1
d

⁢

(

r
c

-

r

a
⁢
b

)

⁢

if
⁢

⁢

r
c

<

r

a
⁢
b

<

r
c

+
d

0

if
⁢

⁢

r

a
⁢
b

<

r
c

+
d

0

if
⁢

⁢
β

wherein,
U ab (r ab ) is the close contact potential between a residue atom a of the first residue and an environmental atom b, d is a non-zero offset, r c , is equal to or greater than a first distance threshold, r ab is the distance between a residue atom a of the first residue and an environmental atom b, βrefers to atoms a and b that are either members of the same residue or that are bonded either directly (1-2 bonded), through one intervening atom (1-3 bonded) or through two intervening atoms (1-4 bonded),
(b) using a computer system to calculate a first contact area of the one or more residue atoms of the first residue of the parent protein that are exposed to the one or more environment atoms as a difference between (i) a total solvent accessible surface area of the one or more residue atoms of the first residue of the parent protein and (ii) a solvent accessible area of the one or more residue atoms of the first residue of the parent protein in the presence of the parent protein, wherein the method further comprises calculating the total solvent accessible surface area of the one or more residue atoms of the first residue of the parent protein and calculating the solvent accessible area of the one or more residue atoms of the first residue of the parent protein in the presence of the parent protein using the computer system,
(c) calculating a first close contact surface density (CCSD) by dividing the summation of the one or more close contact potentials of the parent protein by the first contact area,
(d) mutating in silico one or more residues of the first protein to provide the variant protein,
(e) calculating a summation of one or more close contact potentials of the variant protein based on respective distances between the one or more residue atoms of the first residue of the variant protein and one or more environment atoms of the one or more residue atoms of the first residue of the variant protein in accordance with the close contact potential formula of the calculating (a),
(f) calculating a second contact area of the one or more residue atoms of the first residue of the variant protein that are exposed to the one or more environment atoms as a difference between (i) a total solvent accessible surface area of the one or more residue atoms of the first residue of the variant protein and (ii) the solvent accessible area of the one or more residue atoms of the first residue of the variant protein in the presence of the variant protein,
(g) calculating a second CCSD b

Assignees

• Ohrn Anders
• Zymeworks Inc

Inventors

• Ohrn Anders

Classifications

• G16B5/30 Primary

  Dynamic-time models · CPC title

• G16B15/20

  Protein or domain folding · CPC title

• G16B5/00 Primary

  ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks · CPC title

• G01N33/531

  Production of immunochemical test materials · CPC title

• G01N2500/00

  Screening for compounds of potential therapeutic value · CPC title