Systems and methods for in silico evaluation of polymers

Patent metadata

Field	Value
Publication number	US-2016188789-A1
Application number	US-201414911505-A
Country	US
Kind code	A1
Filing date	Jul 14, 2014
Priority date	Aug 15, 2013
Publication date	Jun 30, 2016
Grant date	—

Abstract

Systems and methods for evaluating a polymer make use of a workflow request identifying input data and a workflow instance. The workflow instance comprises a plurality of actors, each having one or more input and output ports. The workflow instance defines an acyclic directed graph comprising nodes and edges. Each node is an actor in the plurality of actors and each edge corresponds to at least one of (i) an input port of an actor in the plurality of actors and (ii) an output port of an actor in the plurality of actors. Graph parsing produces an ordered list of job requests. Each job request corresponds to an actor in the plurality of actors. An actor in the plurality of actors is executed in an order specified by the ordered list and contributes an output to another actor in the plurality of actors that is specified by the graph.

First claim

What is claimed is:

1 . A method of evaluating a first polymer, the method comprising:
at a computer system having one or more processors and memory storing one or more programs to be executed by the one of more processors: (A) receiving a workflow request, wherein the workflow request identifies (i) a workflow instance and (ii) input data for the workflow instance, the input data comprising a set of three-dimensional coordinates {x 1 , . . . , x N } for all or a portion of the first polymer, wherein each respective x i in {x 1 , . . . , x N } is a three dimensional coordinate for an atom in a first plurality of atoms in the first polymer, and wherein the workflow instance comprises a plurality of actors, each actor in the plurality of actors having at least one input port and at least one output port, wherein the workflow instance defines an acyclic directed graph comprising a plurality of nodes and a plurality of edges, each node in the plurality of nodes being an actor in the plurality of actors and each edge in the plurality of edges corresponding to at least one of (i) an input port of an actor in the plurality of actors and (ii) an output port of an actor in the plurality of actors; (B) assigning a workflow identifier to the workflow request; (C) parsing the acyclic directed graph into an ordered list of job requests, each respective job request in the ordered list of job requests corresponding to an actor in the plurality of actors; (D) executing a first actor in the plurality of actors in accordance with an order specified by the ordered list of job requests, wherein the first actor contributes to the computation of a metric associated with the first polymer; and (E) executing a second actor in the plurality of actors upon completion of the execution of the first actor, wherein the second actor is identified by the acyclic directed graph and a first result of the first actor is passed from an output port of the first actor to an input port of the second actor, wherein the second actor contributes to the computation of the metric associated with the first polymer, thereby evaluating the first polymer.

2 . The method of claim 1 , wherein an actor in the plurality of actors makes a derivation of the first polymer, wherein the derivation is one or more atomic replacements, insertions or deletions within the first polymer.

3 . The method of claim 1 , wherein first polymer comprises a plurality of residues, and wherein an actor in the plurality of actors makes a plurality of derivations of the first polymer, wherein each respective derivation in the plurality of derivations is a replacement, insertion or deletion of one or more residues within the first polymer.

4 . The method of claim 3 , wherein the first polymer is a protein and a derivation in the plurality of derivations is a mutation of one or more residues in the first polymer.

5 . The method of claim 1 , wherein the first polymer is a protein, a polypeptide, a polynucleic acid, a polyribonucleic acid, a polysaccharide, a protein conjugated with one or more therapeutic or diagnostic agents, or an assembly of any combination thereof.

6 . The method of any one of claims 1 - 5 , the method further comprising:
(F) executing a third actor in the plurality of actors upon completion of the execution of the first actor, and concurrent to execution of the second actor, wherein the third actor is identified by the acyclic directed graph and the first result of the first actor is passed from the output port of the first actor to an input port of the third actor, wherein the third actor contributes to the computation of a metric associated with the first polymer.

7 . The method of any one of claims 1 - 6 , wherein the first result comprises a plurality of elements, the second actor is configured to run a plurality of tasks, and each element in the plurality of elements is for a different task in the plurality of tasks in the second actor.

8 . The method of any one of claims 1 - 7 , wherein the input data further comprises an option for the first actor and wherein executing the first actor further comprises providing the first actor with the option through an option port of the first actor.

9 . The method of any one of claims 1 - 8 , wherein the input data for the workflow instance specifies an atomic force field or a rotamer library, and one or more corresponding parameters for the workflow type of the workflow instance.

10 . The method of any one of claims 1 - 9 , wherein the first actor is written in a first programming language and the second actor is written in a second programming language other than the first programming language.

11 . The method of any one of claims 1 - 10 , wherein
each respective input port in each actor in the plurality of actors belongs to an input port class in a plurality of predetermined input port classes, and each respective output port in each actor in the plurality of actors belongs to an output port class in a plurality of predetermined output port classes.

12 . The method of any one of claims 1 - 11 , wherein all or a portion of the workflow request is in the form of an alphanumeric configuration file.

13 . The method of any one of claims 1 - 12 , wherein an actor in the plurality of actors comprises a multi-input port that receives data from a first source and a second source.

14 . The method of claim 13 , wherein the first source is defined by the output port of another actor in the plurality of actors and the second source is a predetermined path to a file.

15 . The method of any one of claims 1 - 14 , wherein an actor in the plurality of actors performs a task selected from the group consisting of a molecular dynamics algorithm for the first polymer or a derivation of the first polymer, a structure refinement algorithm for the first polymer or a derivation of the first polymer, a homology modeling algorithm for the first polymer or a derivation of the first polymer, calculation of an accessible surface area term for the first polymer or a derivation of the first polymer, calculation of a potential energy term for the first polymer or a derivation of the first polymer, calculation of a solvent model for the first polymer or a derivation of the first polymer, calculation of a protein side-chain term for the first polymer or a derivation of the first polymer, calculation of a free volume term for the first polymer or a derivation of the first polymer, calculation of a packing efficiency term for the first polymer or a derivation of the first polymer, calculation of a number of interatomic contacts for the first polymer or a derivation of the first polymer, a structure relaxation and refinement algorithm for the first polymer or a derivation of the first polymer, calculation of conformational sub-states and conformational sampling for the first polymer or a derivation of the first polymer, calculation of conformational flexibility for the first polymer or a derivation of the first polymer, a Monte-Carlo or simulated annealing algorithm for the first polymer or a derivation of the first polymer, calculation of a metric to determine a stability of the first polymer or a derivation of the first polymer, determination of a protonation state of the first polymer or a derivation of the first polymer, and a binding energy calculation for the first polymer or a derivation of the first polymer.

16 . The method of any one of claims 1 - 15 , wherein the plurality of actors comprises three or more actors.

17 . The method of any one of claims 1 - 15 , wherein the plurality of act

Assignees

• Zymeworks Inc

Inventors

• Kisiel Kamil
• Srinivasan Siddharth

Classifications

• G06F19/12 Primary

  Physics · mapped topic

• G16B15/20

  Protein or domain folding · CPC title

• G16B5/00

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

• G16B50/30 Primary

  Data warehousing; Computing architectures · CPC title

• G16B15/00

  ICT specially adapted for analysing two-dimensional [2D] or three-dimensional [3D] molecular structures, e.g. structural or functional relations or structure alignment · CPC title