We report here a novel method for predicting melting temperatures of DNA sequences based on a molecular-level hypothesis on the phenomena underlying the thermal denaturation of DNA. The model presented here attempts to quantify the energetic components stabilizing the structure of DNA such as base pairing, stacking, and ionic environment which are partially disrupted during the process of thermal denaturation. The model gives a Pearson product-moment correlation coefficient (r) of approximately 0.98 between experimental and predicted melting temperatures for over 300 sequences of varying lengths ranging from 15-mers to genomic level and at different salt concentrations. The approach is implemented as a web tool (www.scfbio-iitd.res.in/chemgenome/Tm_predictor.jsp) for the prediction of melting temperatures of DNA sequences.