RAMD

Current version

5.0.4

Description

t-random acceleration molecular dynamics (tRAMD) is a protocol for the ranking of drug candidates by their residence time and obtaining insights into ligand-target dissociation mechanism.
The approach is based on the RAMD method in which, during a standard molecular dynamics simulation of the bound complex, a small additional randomly oriented force is applied to the compound to facilitate its unbinding. Note, that in the previous RAMD versions acceleration (instead of the force) was used as an input parameter.

tRAMD protocol includes:

(i) system minimization and equilibration

(ii) generation of a set of starting replicas using standard MD simulations with NAMD software

(iii) simulations of RAMD trajectories starting from different replicas

(iv) statistical analysis of the RAMD dissociation times using an R script, which yields relative residence times of compounds

Important notice

The RAMD license prohibits commercial use of the code. For testing and using RAMD on a commercial basis you need to negotiate a commercial license by contacting us.

License

Software License Agreement

HITS gGmbH, Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany
– hereinafter referred to as “Licensor” or “HITS gGmbH”-
and person accepting the license agreement on the web page
– hereinafter referred to as “Licensee”-
HITS gGmbH represents both HITS gGmbH and the European Molecular Biology Laboratory,
Meyerhofstrasse 1, 69117 Heidelberg, Germany in this agreement as both parties have
developed parts of the software.

§ 1 Subject Matter of License Agreement

The subject matter of this Agreement is the Software
RAMD
i.e., the latest version available and released for distribution prior to execution of this
Agreement (hereinafter referred to as the “Software”).

§ 2 Shipment

  1. Upon execution of the Agreement, the Software will be shipped electronically.
  2. Licensee will carry out the installation of the Software.

§ 3 License

  1. Licensor grants Licensee the non-exclusive, indefinite right, not limited as to territory, to use
    the Software subject to the provisions set forth below.
  2. Licensee may use the Software only for its own non-commercial research at its own facilities, departments, or institutes. In particular, Licensee shall not allow any third party access to the Software for business or research purposes of third parties.
  3. Licensee shall reproduce the Software only to such extent that is required for the use of the Software in accordance with the terms of this Agreement. Licensee shall make the necessary number of backup copies required for safe operation based on the state of the art, provided, however, that they are marked as backup copies and – to the extent that is technically feasible – the copyright notice has been attached to them.
  1. Licensee will inform the Licensor about any modification made to the licensed
    software.
  2. Licensee shall not grant any sub-licenses to the Software or transfer the Software made
    available to it to any third party. Any use of the Software at a computer center, for the
    provision of outsourcing or application service, requires the express written consent of
    Licensor.

§ 4 Updates

Upon request, Licensor shall supply Licensee with free updates of the major version of the
Software acquired by Licensee. The major version is specified by the first digit in the version
number. The provisions governing the Software shall apply to updates accordingly. The
Licensor is under no obligation to make and release updates.

§ 5 License Fee

  1. In consideration of the provision of the Software and the license grant, Licensee shall acquire
    the rights of use free of charge.

§ 6 Publicity and Exchange of Experience

  1. On its own website, Licensor may identify research projects of Licensee in which the Software
    is used, and/or create links on its own website pointing to the website of Licensee’s project or
    institute.
  2. In publications of Licensee reporting on research projects in which the Software is used,
    Licensee will properly cite by the following references and the version number of the licensed
    software

S. K. Lüdemann, V. Lounnas, R. C. Wade “How Do Substrates Enter and Products Exit the Buried Active Site of Cytochrome P450cam? 2. Steered Molecular Dynamics and Adiabatic Mapping of Substrate Pathways” J. Mol. Biol. 2000303 (5), 813–830

D. B. Kokh, M. Amaral, J. Bomke, U. Grädler, D. Musil, H.-P. Buchstaller, M. K. Dreyer, M. Frech, M. Lowinski, F. Vallee, M. Bianciotto, A. Rak, R. C. Wade “Estimation of drug-target residence times by t-random acceleration molecular dynamics simulations​” submitted to JCTC

§ 7 Duty to Inspect and Notify of Defects

If Licensee is a business person, it shall promptly inspect the Software after receipt in
accordance with § 377 German Trade Code and notify Licensor of any defects that are
apparent during the inspection immediately after delivery, and of any hidden defects
immediately after their discovery. Notice of defect shall be given in writing. Licensee shall
describe the defect(s) in writing and as specifically as possible, to the extent that it may be
reasonably expected to do so.

§ 8 Quality Defects and Defects of Title

  1. Licensor grants the use of Software on an as-is basis. If Software should have defects or
    exhibit unexpected behavior, Licensor does not accept responsibility for removing those
    defects. Licensor also does not accept any responsibility for damages resulting from the use
    of Software.

§ 9 Liability

  1. Under this Agreement and outside the contract, Licensor shall be liable to Licensee without
    restriction in case of willful wrongdoing or in the absence of a warranted quality or durability,
    for gross negligence only in the amount of the typical and foreseeable damages, and in other
    cases, only when a material duty (cardinal duty) has been violated, and in such cases, limited
    to compensation for the foreseeable and typical damages. In all other cases, Licensor does
    not assume any liability.
  2. The liability of Licensor for personal injury and under the Product Liability Act remains
    unaffected by the foregoing liability limitations and restrictions.

§ 10 Statute of Limitations for Claims of Licensee

  1. Any claims of Licensee pursuant to § 8 and § 9 shall fall under the statute of limitations after 1
    (one) year, unless provided otherwise in this Agreement (in particular § 10 par. 5).
  2. In case of quality defects and defects of title, the limitations period shall commence upon delivery of the Software, and in case of other claims for damages or reimbursement of wasted expenditure, at such time when Licensee becomes aware of the circumstances giving rise to the claim or should have become aware of in the absence of gross negligence.
  3. Paragraphs 1 and 2 apply accordingly to claims regarding a refund of the purchase price based on a rescission of contract or reduction of the purchase price, provided, however, that the statute of limitations period shall be no less than three (3) months from the date that an effective notice regarding the rescission or reduction of purchase price has been given.
  4. In any event, the claims shall come under the statute of limitations no later than upon expiration of the maximum periods set forth in § 199 German Civil Code.
  5. Claims based on intentional wrongdoing or the grossly negligent conduct of Licensor, or on a violation of a guarantee given by Licensor or on malice, and claims based on personal injury (life, body, or health) or on the Product Liability Act, shall be subject to the statutory statute of limitations periods.

§ 11 Termination

This agreement is effective until terminated. In case a new version of this license agreement
is published, you will be notified 4 weeks in advance. This agreement will terminate
immediately without notice from HITS gGmbH if you fail to comply with any of the terms and
conditions of this license. This agreement will also terminate immediately without notice from
the HITS gGmbH if it is found to implement patented algorithms or contain copyrighted code
not owned or licensed by HITS for the purpose of its inclusion in the RAMD software. This
agreement cannot be terminated by any other mechanism or for any other reason than those
stated herein.

§ 12 Final Provisions

  1. This Agreement is governed by the law of the Federal Republic of Germany. The application
    of the UN Convention on the Sale of Goods is excluded.
  2. The exclusive venue for all disputes arising from or in connection with this Agreement is Heidelberg, Germany, when the Licensee is a business person, a legal entity governed by public law, or a special fund governed by public law, or does not have a general place of jurisdiction within the Federal Republic of Germany.
  3. This Agreement contains any agreements made between the parties and supersedes any previous agreements. There are no oral collateral agreements. Modifications and amendments of this Agreement must be in writing to be effective. The same applies to a waiver of the mandatory written form requirement.
  4. If any provision of this Agreement is or should become invalid, or if the agreement is incomplete, its remaining terms and provisions shall remain in full force and effect. The invalid provision is deemed to have been replaced with such a provision that economically and validly most closely matches the meaning and purpose of the invalid provision. The same applies to a gap in this Agreement.
  5. Address all correspondence regarding this license to the electronic mail address: mcmsoft@h-its.org. Any inquiries and comments regarding bugs, bug fixes, enhancements, modifications or any other similar issues should also be directed to: mcmsoft@h-its.org