The characterization of biological interfaces is widely recognized as one of the main challenges for modern biology. In particular, biological membranes are nowadays known to be an active environment that allows membrane proteins to perform their work and modulates their function. Integral and peripheral membrane proteins constitute 1/3 of the human proteome, and account for about 50% of the targets of modern medicinal drugs. Despite their remarkable role, their interplay with the membrane is often poorly characterized, mainly because of the limits that the currently available experimental techniques encounter when treating hydrophobic environments. In particular, peripheral membrane proteins are often studied in their soluble version: this approach is highly limiting, as the interaction with the membrane is essential for the activity of these biomolecules. Here, we show the potential of a combined computational-experimental approach in order to overcome the aforementioned limits. In particular, we use molecular modeling to study two peripheral membrane proteins of interest, and successively design ad hoc wet lab experiments to verify the outcomes and predictions of the simulations. This approach allows to bypass the technical limits and high costs of the wet lab techniques, by guiding the experiments with the data of the computational simulations. We focused our attention on the following peripheral membrane proteins: New Delhi metallo-beta-lactamase (NDM-1). NDM-1 is a bacterial enzyme that causes antibiotic resistance. Within the class of metallo-beta-lactamases, it represents the most serious threat to global health. The larger resistance of NDM-1 with respect to other proteins of the same class, has been linked to its post-translational modification, which connects it to the outer bacterial membrane of Gram-negative bacteria: this event can significantly increase the chances of NDM-1 to spread through the infection through vesicles excretion. In the present work, we elucidated the mechanistic aspects of the NDM-1/bacterial membrane interaction, and identified the features that contribute to the efficiency of this mechanism. Golgi phosphorylated protein 3 (Golph3). Golph3 is a peripheral membrane protein present at the Golgi apparatus of most eukaryotic cells. Its normal function consists in binding glycosylating enzymes, and transport them through the Golgi cisternae. In humans, Golph3 has been found to be overexpressed in several forms of cancer: however, no Golph3 inhibitors are currently present in the pharmaceutical market. This is mainly due to the lack of structural information regarding the molecular mechanism of Golph3. Here, we clarify the features of Golph3 that allow it to bind to the Golgi, and elucidate the mechanism of membrane binding. We also propose a recognition mechanism between Golph3 and the glycoenzymes, based on events predicted by the computer simulations. Overall, in the present work we demonstrate the potential of computational-experimental approaches in structural biology, and in particular in the study of peripheral membrane proteins. We show that a combined approach constitutes the best way of overcoming the limits of each technique, and we discuss the repercussions on the study of systems of biological interest.