SSIPe is a method to calculate binding free-energy changes (ΔΔGbind) of protein-protein interactions (PPIs) upon mutations at protein-protein interface. Starting from a PPI complex structure, SSPIe first generates multple structure and sequence alignments from non-redundant interface library (NIL) and STRING databases separately. The structural and sequence profiles are then combined with the physical energy function EvoEF to predict the impact of the mutations on PPI binding free energies. SSIPe can be used to guide the designing and engineering of protein-protein interactions with enhanced binding affinity, and/or for understanding the roles of disease-related mutations associated with protein-protein interactions.
Due to the restriction of uploading large files (> 25 Mb per file), only the source code, binaries and training and test sets are uploaded to this repository. The NIL and STRING databases, which are 1.1 Gb and 2.4 Gb respectively, cannot be uploaded, but they can be found at https://zhanggroup.org/SSIPe/download/. The source code and training/test data are also provided in our website. After the two libraries (NIL and STRING) are downloaded from the website, they can be unzipped and put into the directory /bin/ssip.
SSIPe can only be run in a Linux system. User can download the program and libraries which are mentioned above and directly run the run_SSIPe.pl script following the instructions in example/README. The results will be printed out in result.txt. Before running the program, the user should check if some of the external binaries are executable. Specifically, the user should check:
bin/evoef/EvoEF/src/EvoEF
bin/extint/extint
bin/ssip/ialign/extint
bin/ssip/ialign/IS-align
bin/ssip/ncbi-blast-2.7.1+/bin/psiblast
bin/ssip/ncbi-blast-2.7.1+/bin/makeblastdb
bin/ssip/seqalign/build_cpx_alignment
bin/ssip/seqalign/PDB2FAS
bin/ssip/SSIPserver/SSIP
Due to size restriction, the psibalst and makeblastad program are uploaded as zipped file (.zip), the user can unzip them into the same directory. For the other programs, the user may need to use 'chmod +x' to make the other binaries executable or if neccessary, the user can recompile and build the binaries. For recompiling EvoEF, the user can go to the bin/evoef/EvoEF/src/ directory and run 'g++ -O3 -o EvoEF *.cpp' to rebuild EvoEF. For recompiling SSIP, the user can go to the bin/ssip/SSIPserver/ and run 'g++ -O3 -o SSIP src/*.cpp' to rebuild SSIP.
For SSIPe webserver, the user can refer to https://zhanggroup.org/SSIPe/. Please contact Dr. Xiaoqiang Huang ([email protected] or [email protected]) if you have any question and report any bug about SSIPe.
Huang X, Zheng W, Pearce R, Zhang Y. SSIPe: accurately estimating protein-protein binding affinity change upon mutations using evolutionary profiles in combination with an optimized physical energy function. Bioinformatics (2020) 36:2429-2437.