What is AutoT&T?
The Automatic Tailoring and Transplanting (AutoT&T) method is developed as a versatile computational tool for lead optimization as well as lead discovery in molecular-targeted drug design. This method detects suitable fragments on reference molecules, e.g. outputs of a virtual screening job in prior, and then transplants them onto the given lead compound to generate new ligand molecules. Then, binding affinities, synthetic feasibilities and drug-likeness properties are evaluated to select the promising candidates for further consideration.

AutoT&T represents a new category of de novo design method. Compared to conventional build-up methods, AutoT&T has the following technical advantages: (1) AutoT&T does not reply on a pre-defined built-in library of building blocks. All fragments used in structural operation are truncated directly from other organic molecules. (2) AutoT&T does not need to perform conformational sampling during structural construction. The binding poses of all reference molecules are generated in prior, for example, through a virtual screening job towards the given target protein. In this way, the outcomes of virtual screening can be "recycled" by AutoT&T. (3) AutoT&T is able to conduct a systematic crossover between the lead molecule and all given reference molecules. It thus does not rely on a sampling algorithm to tackle the “combinatorial explosion” problem. Due to the several reasons mentioned above, AutoT&T is not only able to produce more reasonable designs, it is also more efficient than conventional de novo design methods.

AutoT&T version 2
The original version of AutoT&T was published in 2011. Significant improvements have been made since then. The new version, i.e. AutoT&T2, is faster by up to a few thousand folds in a multi-round optimization job. New applications are also implemented in AutoT&T2, for example, performing structural crossover among multiple lead molecules or design of ligand molecules from scratch. Please refer to our latest publication or the user manual for more details.

Click this link for a copy of the user manual of AutoT&T2. [User manual of AutoT&T2]

Demo interface for running AutoT&T2 on-line
Through the interface below, the user can conduct on-line lead optimization jobs by running the AutoT&T2 software at the server end. To submit a job through this web interface, the user is required to upload the necessary inputs, including the structure files of a target protein, a lead molecule, and a reference library. Note that both the lead molecule and the whole reference library need to be docked into the binding site on the target protein in prior. Then, the user may set the parameters included here. Once the job is completed at the server end, a new web page will be displayed for the user to download the results.

Note that the interface below is designed for the user to test AutoT&T2 in the standard running mode, i.e. structural optimization based on a single lead molecule. Users need to download the complete AutoT&T2 software suite to test its full functions. Click here for the input files for running the p38 MAPK test case: [Input files for running the p38 MAPK test case]

Upload Structure Files
(* in PDB Format)
(* in Mol2/SDF Format)
(* in Mol2/SDF Format)
Optional Parameters
Standard optimization on single lead
Maximal rounds of optimization
Method for searching matched bonds:
distance cutoff for matching bond (Angstrom)
Angle cutoff for matching bond (degree)
Maximal molecules retained after each round
Consider A-H bonds in matching
Use RECAP rules to filter matched bonds
PLP scoring function
Enable energy minimization
Method for minimization:
Maximal steps for energy minimization
Ignore electrostatic energy
Method for clustering:
- Hydrogen bond acceptors
- Hydrogen bond donors
- Number of rotatable bonds
- Number of rings
- Number of heavy atoms
- LogP value
Ignore molecules with multi-fragments
  
Obtain the full AutoT&T2 software suite
The AutoT&T2 software suite is available to the public. Please complete [REGISTRATION] first, and then you will be able to download the full package. Upon registration, an end-user license agreement must be signed for the protection of our copyright. The license is free to all academic/governmental users.

The AutoT&T2 package includes the executable and source codes of all major functions, the user manual, and the necessary material for running the several demo examples described in our publication. It is provided as a TAR.GZ package (155 MB in size).

Reference:
  1. Yan Li, Zhixiong Zhao, Zhihai Liu, and Renxiao Wang*, "AutoT&T v2: An Efficient and Versatile Tool for Lead Structure Generation and Optimization", J. Chem. Inf. Model., 2016, in revision. (AutoT&T version 2)
  2. Yan Li, Yuan Zhao, Zhihai Liu, Renxiao Wang*, "Automatic Tailoring and Transplanting: A Practical Method that Makes Virtual Screening More Useful", J. Chem. Inf. Model., 2011, Vol. 51 (6), pp 1474-1491. (AutoT&T version 1)


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