Identification of potential dipeptidyl peptidase IV inhibitors from the ConMedNP library by virtual screening, and molecular dynamics methods
Hans Merlin Tsahnang Fofack,
Maraf Mbah Bake,
Simon Petry,
Baruch A. Ateba,
Pascal Amoa Onguéné,
Haydar Mohammad-Salim,
Fidele Ntie-Kang,
Luc Meva'a Mbaze,
Serhii Vakal,
Cyril A Kenfack
Affiliations
Hans Merlin Tsahnang Fofack
Laboratoire Optique et Applications, Centre de Physique Atomique Moleculaire et Optique Quantique, Faculte des Sciences, Université de Douala, B.P. 8580, Douala, Cameroon; Analytical, Structural and Materials Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Douala, B.P. 24157, Douala, Cameroon
Maraf Mbah Bake
Physical and Theoretical Chemistry Unit, Laboratory of applied Physical and Analytical Chemistry, Faculty of Science, University of Yaoundé I, P.O. BOX 812, Yaoundé, Cameroon; Computational Chemistry Laboratory, Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon; Corresponding authors.
Simon Petry
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 3, 14195, Berlin, Germany
Baruch A. Ateba
Laboratoire Optique et Applications, Centre de Physique Atomique Moleculaire et Optique Quantique, Faculte des Sciences, Université de Douala, B.P. 8580, Douala, Cameroon; Analytical, Structural and Materials Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Douala, B.P. 24157, Douala, Cameroon
Pascal Amoa Onguéné
University Institute of Wood technology, Mbalmayo, Cameroon
Haydar Mohammad-Salim
Department of Chemistry, Faculty of Science, University of Zakho, Zakho, Duhok, 42001, Kurdistan Region, Iraq; Molecular Topology and Drug Design Research Unit, Department of Physical Chemistry, Pharmacy Faculty, University of Valencia, 46100, Valencia, Spain
Fidele Ntie-Kang
Center for Drug Discovery, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon; Department of Chemistry, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon; Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, Kurt-Mothes Strasse 3, 06120, Halle (Saale), Germany
Luc Meva'a Mbaze
Physical and Theoretical Chemistry Laboratory, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Corresponding author.
Serhii Vakal
Structural Bioinformatics Lab, Faculty of Science and Engineering, Åbo Akademi University, Tuomiokirkontori 3, 20500, Turku, Finland; Corresponding authors.
Cyril A Kenfack
Laboratoire Optique et Applications, Centre de Physique Atomique Moleculaire et Optique Quantique, Faculte des Sciences, Université de Douala, B.P. 8580, Douala, Cameroon; Corresponding author.
In this study, we screened novel dipeptidyl peptidase IV (DPP4) inhibitors from the ConMedNP library consisting of 3507 molecules. Interestingly, molecular docking, ADMET, and the anti-diabetic activity predictions suggest that three molecules, namely OTH_UD_XX06_1, GB19, and BMC_000104, have a high binding affinity toward DPP4. The molecular dynamics (MD) simulation results suggest that these hit molecules have a stable binding pose and occupy the binding pockets throughout the 200 ns simulation. The presence of intermolecular H-bonding between the ligands and DPP4 was observed throughout the simulation period. Thus, docking and MD results, predicted that the three compounds were the most potent DPP4 inhibitors that could putatively bind to the DPP4 active site via both conventional H-bonding and hydrophobic interactions. These results could aid the discovery of new drugs to treat type 2 diabetes.
