Investigators
Markus Buehler, David Kaplan
Contact info (email)
mbuehler@mit.edu, david.kaplan@tufts.edu
1. Define context(s)
reveal new biological insights
Current Conformance Level / Target Conformance Level
Extensive
Primary goal of the model/tool/database
Silk project;
-Replica exchange molecular dynamics is used to develop a structure for the silk chimeras.
-MD is also used to explain the change in integrin folding associated with its activation due to interactions with inorganic surfaces
Silk elastin project:
- Replica exchange molecular dynamics to guide design of elastin domains in SELPs (silk elastin like proteins)
Biological domain of the model
Protein
Structure(s) of interest in the model
Silk - silica chimeras, silk elastin proteins
Spatial scales included in the model
Protein modeled atomistically
Time scales included in the model
10 ns REMD, 20 ns MD
2. Data for building and validating the model
| Data for building the model | Published? | Private? | How is credibility checked? | Current Conformance Level / Target Conformance Level |
|---|---|---|---|---|
| in vitro (primary cells cell, lines, etc.) | ||||
| ex vivo (excised tissues) | ||||
| in vivo pre-clinical (lower-level organism or small animal) | ||||
| in vivo pre-clinical (large animal) | ||||
| Human subjects/clinical | ||||
| Other: ________________________ | experimental results | Extensive |
| Data for validating the model | Published? | Private? | How is credibility checked? | Current Conformance Level / Target Conformance Level |
|---|---|---|---|---|
| in vitro (primary cells cell, lines, etc.) | ||||
| ex vivo (excised tissues) | ||||
| in vivo pre-clinical (lower-level organism or small animal) | ||||
| in vivo pre-clinical (large animal) | ||||
| Human subjects/clinical | ||||
| Other: ________________________ | experimental results | experimental results | Extensive |
3. Validate within context(s)
| Who does it? | When does it happen? | How is it done? | Current Conformance Level / Target Conformance Level | |
|---|---|---|---|---|
| Verification | Prof. Guy Genin | April 2020 | Reading and verifying appropriateness of computational methods from paper | Extensive |
| Validation | Prof. Guy Genin | April 2020 | Running simulations independently in GROMACS using provided input files | Extensive |
| Uncertainty quantification | Prof. Guy Genin | April 2020 | Additional replicas will be run to determine levels of fluctuation in results | Extensive |
| Sensitivity analysis | Prof. Guy Genin | April 2020 | Extensive | |
| Other:__________ | ||||
| Additional Comments | we have transferred all the simulation files, have been going through email correspondence on questions of how to run the REMD code | Extensive |
4. Limitations
| Disclaimer statement (explain key limitations) | Who needs to know about this disclaimer? | How is this disclaimer shared with that audience? | Current Conformance Level / Target Conformance Level |
|---|---|---|---|
| REMD methods can be used across many different protein sequences. Limitation in implementation based on computational resources available to researchers | Other researchers planning to run similar simulations | Through the MCP | Extensive |
| Running simulations for extended time periods comes at great computational cost | People running simulations; Generally known in field | Generally known in field | Extensive |
5. Version control
| Current Conformance Level / Target Conformance Level |
|---|
| Extensive |
| Naming Conventions? | Repository? | Code Review? | |
|---|---|---|---|
| individual modeler | No convention | No | |
| within the lab | N/A | N/A | |
| collaborators | Validator "_xj" | No |
6. Documentation
| Current Conformance Level / Target Conformance Level | |
|---|---|
| Code commented? | Extensive |
| Scope and intended use described? | Extensive |
| User’s guide? | Extensive (through the form of a powerpoint) |
| Developer’s guide? | Extensive |
7. Dissemination
| Current Conformance Level / Target Conformance Level |
|---|
| Extensive |
| Target Audience(s): | “Inner circle” | Scientific community | Public |
|---|---|---|---|
| Simulations | Link to repository | DOI: 10.1002/adfm.201702570 / DOI: 10.1002/adfm.201600236 | |
| Models | execution input scripts | publications | |
| Software | Available to group members | Open source GROMACS program | |
| Results | DOI: 10.1002/adfm.201702570 / DOI: 10.1002/adfm.201600236 | ||
| Implications of results | DOI: 10.1002/adfm.201702570 / DOI: 10.1002/adfm.201600236 |
8. Independent reviews
| Current Conformance Level / Target Conformance Level |
|---|
| Partial |
| Reviewer(s) name & affiliation: | Prof. Guy Genin, Washington University in St.Louis |
|---|---|
| When was review performed? | April 2020 |
| How was review performed and outcomes of the review? | in progress |
9. Test competing implementations
| Current Conformance Level / Target Conformance Level |
|---|
| Adequate |
| Yes or No (briefly summarize) | |
|---|---|
| Were competing implementations tested? | Yes |
| Did this lead to model refinement or improvement? | Yes |
10. Conform to standards
| Current Conformance Level / Target Conformance Level |
|---|
| Extensive |
| Yes or No (briefly summarize) | |
|---|---|
| Are there operating procedures, guidelines, or standards for this type of multiscale modeling? | Yes; Detailed instructions for simulation methods have been included in the main text of the papers. |
| How do your modeling efforts conform? | Modeling code is commented and provided in NIH repository |