Analyzing VEGFA/VEGFR1 Interaction: Application of the Resonant Recognition Model-Stockwell Transform Method to Explore Potential Therapeutics for Angiogenesis-Related Diseases.

Abstract

The interaction between vascular endothelial growth factor A (VEGFA) and VEGF receptor 1(VEGFR1) is a central focus for drug development in pathological angiogenesis, where aberrant angiogenesis underlies various anomalies necessitating therapeutic intervention. Identifying hotspots of these proteins is crucial for developing new therapeutics. Although machine learning techniques have succeeded significantly in prediction tasks, they struggle to pinpoint hotspots linked to angiogenic activity accurately. This study involves the collection of diverse VEGFA and VEGFR1 protein sequences from various species via the UniProt database. Electron-ion interaction Potential (EIIP) values were assigned to individual amino acids and transformed into frequency-domain representations using discrete Fast Fourier Transform (FFT). A consensus spectrum emerged by consolidating FFT data from multiple sequences, unveiling specific characteristic frequencies. Subsequently, the Stockwell Transform (ST) was employed to yield the hotspots. The Resonant Recognition Model (RRM) identified a characteristic frequency of 0.128007 with an associated wavelength of 1570 nm and RRM-ST identified hotspots for VEGFA (Human 36, 46, 48, 67, 71, 74, 82, 86, 89, 93) and VEGFR1 (Human 224, 259, 263, 290, 807, 841, 877, 881, 885, 892, 894, 909, 913, 1018, 1022, 1026, 1043). These findings were cross-validated by Hotspots Wizard 3.0 webserver and Protein Data Bank (PDB). The study proposes using a 1570 nm wavelength for photo bio modulation to boost VEGFA/VEGFR1 interaction in the condition that is needed. It also aims to reduce VEGFA/VEGFR2 interaction, limiting harmful angiogenesis in conditions like diabetic retinopathy. Also, the identified hotspots assist in designing agonistic or antagonistic peptides tailored to specific medical requirements with abnormal angiogenesis.