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
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
i.e., the latest version available and released for distribution prior to execution of this
Agreement (hereinafter referred to as the “Software”).
§ 2 Shipment
Upon execution of the Agreement, the Software will be shipped electronically.
Licensee will carry out the installation of the Software.
§ 3 License
Licensor grants Licensee the non-exclusive, indefinite right, not limited as to territory, to use
the Software subject to the provisions set forth below.
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.
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.
Licensee will inform the Licensor about any modification made to the licensed
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
§ 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
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
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
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
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. 2000, 303 (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
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
§ 9 Liability
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.
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
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).
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.
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.
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.
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
§ 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
§ 12 Final Provisions
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.
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.
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.
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.
Address all correspondence regarding this license to the electronic mail address:
email@example.com. Any inquiries and comments regarding bugs, bug fixes, enhancements,
modifications or any other similar issues should also be directed to: